Based on the research of a biological olfactory system, a novel chaotic neural network model - K set model has been es- tablished. This chaotic neural network not only simulates the real brain activity of an olfactor...Based on the research of a biological olfactory system, a novel chaotic neural network model - K set model has been es- tablished. This chaotic neural network not only simulates the real brain activity of an olfactory system, but also presents a novel chaotic concept for signal processing and pattern recognition. The characteristics of the K set models are investigated and show that a KIII model can be used for image pattern classification.展开更多
How do individual neurons develop and how are they in- tegrated into neuronal circuitry？ To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult li...How do individual neurons develop and how are they in- tegrated into neuronal circuitry？ To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult life. A neural stem cell must go through several stages of maturation, including proliferation, migration, differentiation, and integration, to become fully embedded to an existing neuronal circuit. The knowledge on this topic so far has come mainly from cell culture studies. Studying the development of individual neurons within intact neuronal networks in vivo is inherently difficult. Most neurons are generated form neural stem cells during embryonic and early postnatal development.展开更多
OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, ...OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.展开更多
Atmospheric CO2 can signal the presence of food, predators or environmental stress and trigger stereotypical behaviors in both vertebrates and invertebrates. Recent studies have shown that the necklace olfactory syste...Atmospheric CO2 can signal the presence of food, predators or environmental stress and trigger stereotypical behaviors in both vertebrates and invertebrates. Recent studies have shown that the necklace olfactory system in mice sensitively detects CO2 in the air. Olfactory CO2 neurons are believed to rely on cyclic gnanosine monophosphate （cGMP） as the key second messenger; however, the specific ion channel underlying CO2 responses remains unclear. Here we show that CO2-evoked neuronal and behavioral responses require cyclic nucleotide-gated （CNG） channels consisting of the CNGA3 subunit. Through Ca2＋-imaging, we found that CO2-triggered Ca2＋ influx was abolished in necklace olfactory sensory neurons （OSNs） of CNGA3-knockout mice. Olfactory detection tests using a Go/No-go paradigm showed that these knockout mice failed to detect 0.5% CO2. Thus, sensitive detection of atmospheric CO2 depends on the function of CNG channels consisting of the CNGA3 subunit in necklace OSNs. These data support the important role of the necklace olfactory system in CO2 sensing and extend our understanding of the signal transduction pathway mediating CO2 detection in mammals [Current Zoology 56 （6）： 793-799, 2010].展开更多
Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory syste...Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NF𝜅B neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.展开更多
Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets i...Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets in Bactrocera dorsalis, also known as the functional study of key olfactory genes, relies on CRISPR/Cas9-mediated gene knockout techniques. However, these techniques face limitations when applied to lethal genes. Transgenic technology offers a solution since it enables precise manipulation of gene expression in specific tissues or during certain developmental stages. Consequently, this study developed a piggyBac-mediated transgenic system in B. dorsalis to investigate reporter gene expression in olfactory organs, and assessed the olfactory behavior andantennal electrophysiological responses in transgenic lines. The goal was to assess the potential of this approach for future research on olfactory gene function. A universally expressed housekeeping gene from the BdorActin family was identified using the developmental transcriptome dataset. Its candidate promoter region(BdorActinA3a-1^(P–2k)) was then cloned into the piggyBac plasmid. We subsequently established two stable transgenic lines with specific TTAA insertion sites on chromosomes 4 and 5, consistent with the characteristics of piggyBac transposition. The transgenic strains exhibited essentially normal survival, with hatchability and adult lifespan unaffected, althoughthere were slight reductions in the emergence rate and oviposition capacity. The fluorescent reporter has been successfully expressed in olfactory-related organs, such as the antennae, proboscis, maxillary palp, legs, external genitalia, and brain. The antennal electrophysiological responses to representative chemicals in the transgenic lines were consistent with those of the wild type. However, some olfactory-related behaviors, such as pheromone response and mating, were significantly affected in the transgenic lines. These findings suggest that our system could potentially be applied in future olfactory research, such as driving the expression of exogenous elements that are effective in olfactory organs. However, caution is advised regarding its impact when applied to some olfactoryrelated behavioral phenotypes.展开更多
A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy a...A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.展开更多
Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which th...Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying therapies.The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons.In this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the brain.We review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and signs.Finally,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.展开更多
Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropatholog...Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropathologically,both are proteinopathies with pathological aggregates(plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease,and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease).These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages.Both disorders present a long prodromal period,characterized by preclinical signs including hyposmia.Interestingly,the olfactory system,particularly the anterior olfactory nucleus,is initially and preferentially affected by the pathology.Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes.It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding(seeding),which then propagates through neurons and glia(spreading).Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading.Connectomic approaches reveal a number of hubs in the olfactory system(anterior olfactory nucleus,olfactory entorhinal cortex and cortical amygdala)that are key interconnectors with the main hubs(the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus)of network dysfunction in Alzheimer’s and Parkinson’s diseases.展开更多
Tolfactory system of adult lepidopterans is among the best described neuronal circuits.However,comparatively little is known about the organization of the olfactory system in the larval stage of these insects.Here,we ...Tolfactory system of adult lepidopterans is among the best described neuronal circuits.However,comparatively little is known about the organization of the olfactory system in the larval stage of these insects.Here,we explore the expression of olfactory receptors and the organization of olfactory sensory neurons in caterpillars of Pieris brassicae,a significant pest species in Europe and a well-studied species for its chemical ecology.To describe the larval olfactory system in this species,we first analyzed the head transcriptome of third-instar larvae(L3)and identified 16 odorant receptors(ORs)including the OR coreceptor(Orco),13 ionotropic receptors(IRs),and 8 gustatory receptors(GRs).We then quantified the expression of these 16 ORs in different life stages,using qPCR,and found that the majority of ORs had significantly higher expression in the L4 stage than in the L3 and L5 stages,indicating that the larval olfactory system is not static throughout caterpillar development.Using an Orco-specific antibody,we identified all olfactory receptor neurons(ORNs)expressing the Orco protein in L3,L4,and L5 caterpillars and found a total of 34 Orco-positive ORNs,distributed among three sensilla on the antenna.The number of Orco-positive ORNs did not differ among the three larval instars.Finally,we used retrograde axon tracing of the antennal nerve and identified a mean of 15 glomeruli in the larval antennal center(LAC),suggesting that the caterpillar olfactory system follows a similar design as the adult olfactory system,although with a lower numerical redundancy.Taken together,our results provide a detailed analysis of the larval olfactory neurons in P brassicae,highlighting both the differences as well as the commonalities with the adult olfactory system.These findings contribute to a better understanding of the development of the olfactory system in insects and its life-stage-specific adaptations.展开更多
Simulating biological olfactory neural system, KⅢnetwork, which is a high-dimensional chaotic neural network, is designed in this paper. Different from conventional artificial neural network, the KⅢnetwork works...Simulating biological olfactory neural system, KⅢnetwork, which is a high-dimensional chaotic neural network, is designed in this paper. Different from conventional artificial neural network, the KⅢnetwork works in its chaotic trajectory. It can simulate not only the output EEG waveform observed in electrophysiological experiments, but also the biological intelligence for pattern classification. The simulation analysis and application to the recognition of handwriting numerals are presented here. The classification performance of the KⅢnetwork at different noise levels was also investigated.展开更多
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventual...Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventually damages the structure of the olfactory epithelium,leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Method Two investigators independently searched four databases consisting of PubMed,ProQuest,Scopus,and Web of Science for relevant records as of November 11,2020 with no time,space,and language restrictions.Google Scholar was also searched for the related resources within the time limit of 2020.All the found articles were reviewed based on the PRISMA flow diagram.Qualitative studies,case reports,editorials,letters,and other non-original studies were excluded from this systematic analysis.Results Initial search yielded 434 records.After reviewing the titles and abstracts,we selected 74 articles;finally,8 articles were depicted to be investigated and read in full text.The obtained results showed an increase in the width and volume of the olfactory cleft(OC),complete or partial destruction of OC,and complete occlusion of OC in COVID-19 patients.Deformation and degeneration as well as a subtle asymmetry were evident in the OBs.Computed tomography(CT),meganetic resonance imaging(MRI),and positron emission tomography(PET)were used to detect the outcomes of anosmia in these studies.Conclusions The changes in OC are greater than those in OB in patients with COVID-19,mainly due to the inflammatory and immune responses in OC.However,fewer changes in OB are due to neurological or vascular disorders.Topical steroid therapy and topical saline can be helpful.展开更多
The engineered biomimetic sensors can not only realize the action of organs,but also combine functional materials as in vitro organs by simulating the response of biological organs to different environmental signals.A...The engineered biomimetic sensors can not only realize the action of organs,but also combine functional materials as in vitro organs by simulating the response of biological organs to different environmental signals.Artificial nose is a concept proposed by imitating biological olfactory system,simulating olfactory nerve cells,olfactory bulb and olfactory cortex through different materials to realize olfactory function.The sensor array used to sense external gas stimulation can be analyzed based on different recognition principles through different original signals such as optics,electricity,electrochemistry and bioelectricity.Furthermore,combined with pattern recognition and microarray technology,artificial nose can be highly integrated with biocompatible and other important properties to achieve in vitro application.The design principle and necessary components of artificial nose are introduced in this paper including sensing structure,recognition system and functional module.At the same time,the potential development prospects of molecular recognition technology,polymer-based materials and microarray integration in artificial nose are prospected.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
We investigated the role of the main olfactory and accessory olfactory systems （MOS and AOS respectively） in the detection of androstenone. We used the following experimental approaches： behavioral, surgical remova...We investigated the role of the main olfactory and accessory olfactory systems （MOS and AOS respectively） in the detection of androstenone. We used the following experimental approaches： behavioral, surgical removal of the vomeronasal organ （VNX） followed by histochemical verification and Fos immunohistochemistry. Using a Y-maze paradigm we estimated sensitivity of NZB/B1NJ and CBA/J mice to androstenone. CBA mice were 2,000-fold more sensitive to androstenone than NZB mice. VNX caused a 4-tol6-fold decrease in sensitivity to androstenone in highly-sensitive CBA mice, but did not affect thresholds in NZB mice. Results indicate the involvement of the MOS and AOS in the detection of androstenone. We observed a specific pattern of Fos-positive cells in the main olfactory bulb of CBA mice but not in NZB mice subsequent to exposure of mice to androstenone; the compound activated cells in the accessory olfactory bulb in both strains of mice, indicating the involvement of the vomeronasal organ. Patterns of Fos-positive cells in the vomeronasal organ were recorded subsequent to exposure to androstenone. Fos-positive receptor cells in the vomeronasal organ of CBA and NZB mice were different, in CBA mice Fos-positive cells were noted in both the basal and apical zones, however, in NZB mice activation was observed only in the apical zone [Current Zoology 56 （6）： 813-818, 2010].展开更多
Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate wit...Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate with OR gene number,though debate exists on whether the number of total ORs,functional ORs,or the percentage of pseudogenes matters most.While olfaction has been poorly studied in most birds,Turkey Vultures(Cathartes aura)demonstrate keen olfactory ability,capable of foraging using smell alone.In contrast,Black Vultures(Coragyps atratus)have been thought to primarily use vision to locate food.Comparison of the OR genes in these two New World vultures presents an opportunity to examine the dynamics of OR evolution in related avian species that may differ in olfactory abilities.Using a PCR and cloning approach with degenerate primers,we sampled the OR subgenome in Turkey and Black Vultures,as well as Red-tailed Hawks(Buteo jamaicensis)and the distantly related Chicken(Gallus gallus),neither of which are thought to use olfaction extensively.Our results indicate that Turkey Vultures have many more OR genes than Red-tailed Hawks or chickens.Surprisingly,Black Vultures had an intermediate number of OR genes.The number of OR genes we estimated in the Turkey Vulture was much greater than previously reported in studies that used short-read sequencing.Additionally,we found that OR genes from New World vultures and Red-tailed Hawks form clades that were distinct from the clade that included most chicken OR genes,indicating that chickens share few OR orthologs with New World vultures or hawks.As previously observed in other animal groups,pseudogenes appeared throughout all clades and their percentage varied among taxa.These findings suggest the OR gene family is highly dynamic,changing rapidly over evolutionary time,and that taxa may have distinct suites of ORs in their genomes.展开更多
BACKGROUND Congenital olfactory disorders(CODs)are rare but impactful conditions that impair the sense of smell from birth.These disorders can significantly affect a child’s appetite,nutrition,safety awareness,and ov...BACKGROUND Congenital olfactory disorders(CODs)are rare but impactful conditions that impair the sense of smell from birth.These disorders can significantly affect a child’s appetite,nutrition,safety awareness,and overall quality of life.Despite their clinical importance,treatment options for CODs remain limited and largely ineffective,with no established therapies capable of restoring olfactory function in pediatric patients.Recent advances in regenerative medicine and stem cell therapy offer promising avenues for addressing sensory deficits.Nasal epithelial stem cells have emerged as a viable candidate for therapeutic intervention due to their accessibility and intrinsic ability to differentiate into olfactory sensory neurons.Preliminary studies suggest their potential in promoting the re-generation of the olfactory epithelium and functional recovery.However,long-term data on the efficacy and safety of such approaches in children are lacking.AIM To evaluate the long-term efficacy and safety of autologous nasal epithelial stem cell transplantation for the treatment of CODs in children.METHODS This prospective,single-center study enrolled 50 children aged 3-15 years with CODs.All patients underwent autologous nasal epithelial stem cell transplantation and were followed up for 3 years.The primary outcome measure was change in olfactory function,assessed using the Sniffin’Sticks test and the University of Pennsylvania Smell Identification Test-Children’s Version.Secondary outcomes included quality of life(measured by the Pediatric Quality of Life Inventory™and a custom olfaction-specific questionnaire),safety,endoscopic evaluation,and electro-olfactogram measurements.Data were analyzed using repeated measures analysis of variance,Friedman’s test,and multiple regression analysis.RESULTS The mean composite olfactory score increased from 8.3±4.7 at baseline to 52.6±18.9 at the 3-year follow-up(P<0.001).Significant improvement(≥50%increase in score)was observed in 60%of patients,with 24%showing moderate improvement.Quality of life scores improved significantly across all domains(P<0.001).No serious adverse events were reported.Minor complications occurred in 16%of patients,which resolved within 2 weeks.Endoscopic evaluation revealed normal-appearing olfactory epithelium in 84%of patients at 3 years,compared to 24%at baseline(P<0.001).Electro-olfactogram amplitudes increased from 0.11±0.08 mV to 0.67±0.31 mV(P<0.001).Age at intervention(β=0.31,P=0.02)and baseline residual olfactory function(β=0.45,P<0.001)were positively associated with treatment outcomes.CONCLUSION Autologous nasal epithelial stem cell transplantation demonstrates significant and sustained improvements in olfactory function and quality of life in children with CODs,with a favorable safety profile over a 3-year follow-up period.This approach represents a promising advancement in the treatment of pediatric sensory disorders.展开更多
文摘Based on the research of a biological olfactory system, a novel chaotic neural network model - K set model has been es- tablished. This chaotic neural network not only simulates the real brain activity of an olfactory system, but also presents a novel chaotic concept for signal processing and pattern recognition. The characteristics of the K set models are investigated and show that a KIII model can be used for image pattern classification.
基金supported by DFG Schwerpunkt program 1392(project MA 4113/2-2)cluster of Excellence and DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain(project B1-9)+1 种基金the German Ministry of Research and Education(BMBFproject 1364480)
文摘How do individual neurons develop and how are they in- tegrated into neuronal circuitry？ To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult life. A neural stem cell must go through several stages of maturation, including proliferation, migration, differentiation, and integration, to become fully embedded to an existing neuronal circuit. The knowledge on this topic so far has come mainly from cell culture studies. Studying the development of individual neurons within intact neuronal networks in vivo is inherently difficult. Most neurons are generated form neural stem cells during embryonic and early postnatal development.
基金Supported by a Grant from the National Natural Sciences Foundation of China(No.30973792)
文摘OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.
基金supported by the China Ministry of Science and Technology 973 (2010CB833902)863 grants (2008AA022902)
文摘Atmospheric CO2 can signal the presence of food, predators or environmental stress and trigger stereotypical behaviors in both vertebrates and invertebrates. Recent studies have shown that the necklace olfactory system in mice sensitively detects CO2 in the air. Olfactory CO2 neurons are believed to rely on cyclic gnanosine monophosphate （cGMP） as the key second messenger; however, the specific ion channel underlying CO2 responses remains unclear. Here we show that CO2-evoked neuronal and behavioral responses require cyclic nucleotide-gated （CNG） channels consisting of the CNGA3 subunit. Through Ca2＋-imaging, we found that CO2-triggered Ca2＋ influx was abolished in necklace olfactory sensory neurons （OSNs） of CNGA3-knockout mice. Olfactory detection tests using a Go/No-go paradigm showed that these knockout mice failed to detect 0.5% CO2. Thus, sensitive detection of atmospheric CO2 depends on the function of CNG channels consisting of the CNGA3 subunit in necklace OSNs. These data support the important role of the necklace olfactory system in CO2 sensing and extend our understanding of the signal transduction pathway mediating CO2 detection in mammals [Current Zoology 56 （6）： 793-799, 2010].
基金supported by the National Natural Science Foundation of China(Nos.22236006,22076146 and 22036001).
文摘Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NF𝜅B neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.
基金the support from the Shenzhen Science and Technology Program, China (KQTD2018041 1143628272)the special funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District, China (PT202101-02)the National Key Research and Development Program of China (2022YFD1700201)。
文摘Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets in Bactrocera dorsalis, also known as the functional study of key olfactory genes, relies on CRISPR/Cas9-mediated gene knockout techniques. However, these techniques face limitations when applied to lethal genes. Transgenic technology offers a solution since it enables precise manipulation of gene expression in specific tissues or during certain developmental stages. Consequently, this study developed a piggyBac-mediated transgenic system in B. dorsalis to investigate reporter gene expression in olfactory organs, and assessed the olfactory behavior andantennal electrophysiological responses in transgenic lines. The goal was to assess the potential of this approach for future research on olfactory gene function. A universally expressed housekeeping gene from the BdorActin family was identified using the developmental transcriptome dataset. Its candidate promoter region(BdorActinA3a-1^(P–2k)) was then cloned into the piggyBac plasmid. We subsequently established two stable transgenic lines with specific TTAA insertion sites on chromosomes 4 and 5, consistent with the characteristics of piggyBac transposition. The transgenic strains exhibited essentially normal survival, with hatchability and adult lifespan unaffected, althoughthere were slight reductions in the emergence rate and oviposition capacity. The fluorescent reporter has been successfully expressed in olfactory-related organs, such as the antennae, proboscis, maxillary palp, legs, external genitalia, and brain. The antennal electrophysiological responses to representative chemicals in the transgenic lines were consistent with those of the wild type. However, some olfactory-related behaviors, such as pheromone response and mating, were significantly affected in the transgenic lines. These findings suggest that our system could potentially be applied in future olfactory research, such as driving the expression of exogenous elements that are effective in olfactory organs. However, caution is advised regarding its impact when applied to some olfactoryrelated behavioral phenotypes.
文摘A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.
文摘Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying therapies.The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons.In this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the brain.We review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and signs.Finally,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.
基金Funding agencies:Sponsored by the Spanish Ministry of Economy and Competitiveness/ERDF(grant no.SAF2016–75768-R)the Autonomous Government of Castilla-La Mancha/ERDF(grant no.SBPLY/17/180501/000430)to AMM.
文摘Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropathologically,both are proteinopathies with pathological aggregates(plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease,and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease).These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages.Both disorders present a long prodromal period,characterized by preclinical signs including hyposmia.Interestingly,the olfactory system,particularly the anterior olfactory nucleus,is initially and preferentially affected by the pathology.Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes.It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding(seeding),which then propagates through neurons and glia(spreading).Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading.Connectomic approaches reveal a number of hubs in the olfactory system(anterior olfactory nucleus,olfactory entorhinal cortex and cortical amygdala)that are key interconnectors with the main hubs(the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus)of network dysfunction in Alzheimer’s and Parkinson’s diseases.
基金financed by a VENI grant(016.Veni.192.116)of the Dutch Research Council(NWO)to AHa China Scholarship Council grant(no.201903250092)to QW.
文摘Tolfactory system of adult lepidopterans is among the best described neuronal circuits.However,comparatively little is known about the organization of the olfactory system in the larval stage of these insects.Here,we explore the expression of olfactory receptors and the organization of olfactory sensory neurons in caterpillars of Pieris brassicae,a significant pest species in Europe and a well-studied species for its chemical ecology.To describe the larval olfactory system in this species,we first analyzed the head transcriptome of third-instar larvae(L3)and identified 16 odorant receptors(ORs)including the OR coreceptor(Orco),13 ionotropic receptors(IRs),and 8 gustatory receptors(GRs).We then quantified the expression of these 16 ORs in different life stages,using qPCR,and found that the majority of ORs had significantly higher expression in the L4 stage than in the L3 and L5 stages,indicating that the larval olfactory system is not static throughout caterpillar development.Using an Orco-specific antibody,we identified all olfactory receptor neurons(ORNs)expressing the Orco protein in L3,L4,and L5 caterpillars and found a total of 34 Orco-positive ORNs,distributed among three sensilla on the antenna.The number of Orco-positive ORNs did not differ among the three larval instars.Finally,we used retrograde axon tracing of the antennal nerve and identified a mean of 15 glomeruli in the larval antennal center(LAC),suggesting that the caterpillar olfactory system follows a similar design as the adult olfactory system,although with a lower numerical redundancy.Taken together,our results provide a detailed analysis of the larval olfactory neurons in P brassicae,highlighting both the differences as well as the commonalities with the adult olfactory system.These findings contribute to a better understanding of the development of the olfactory system in insects and its life-stage-specific adaptations.
文摘Simulating biological olfactory neural system, KⅢnetwork, which is a high-dimensional chaotic neural network, is designed in this paper. Different from conventional artificial neural network, the KⅢnetwork works in its chaotic trajectory. It can simulate not only the output EEG waveform observed in electrophysiological experiments, but also the biological intelligence for pattern classification. The simulation analysis and application to the recognition of handwriting numerals are presented here. The classification performance of the KⅢnetwork at different noise levels was also investigated.
文摘Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection.In anosmic patients,SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb(OB),which eventually damages the structure of the olfactory epithelium,leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Method Two investigators independently searched four databases consisting of PubMed,ProQuest,Scopus,and Web of Science for relevant records as of November 11,2020 with no time,space,and language restrictions.Google Scholar was also searched for the related resources within the time limit of 2020.All the found articles were reviewed based on the PRISMA flow diagram.Qualitative studies,case reports,editorials,letters,and other non-original studies were excluded from this systematic analysis.Results Initial search yielded 434 records.After reviewing the titles and abstracts,we selected 74 articles;finally,8 articles were depicted to be investigated and read in full text.The obtained results showed an increase in the width and volume of the olfactory cleft(OC),complete or partial destruction of OC,and complete occlusion of OC in COVID-19 patients.Deformation and degeneration as well as a subtle asymmetry were evident in the OBs.Computed tomography(CT),meganetic resonance imaging(MRI),and positron emission tomography(PET)were used to detect the outcomes of anosmia in these studies.Conclusions The changes in OC are greater than those in OB in patients with COVID-19,mainly due to the inflammatory and immune responses in OC.However,fewer changes in OB are due to neurological or vascular disorders.Topical steroid therapy and topical saline can be helpful.
基金supported by Natural Science Foundation of Xin-jiang(2022D01E03)National Natural Science Foundation of China(21974150,U1903306)+1 种基金the Youth Innovation Promotion Association,CAS(NO.2018474)Key Research Program of Frontier Sciences(CAS Grant No.ZDBS-LY-JSC029).
文摘The engineered biomimetic sensors can not only realize the action of organs,but also combine functional materials as in vitro organs by simulating the response of biological organs to different environmental signals.Artificial nose is a concept proposed by imitating biological olfactory system,simulating olfactory nerve cells,olfactory bulb and olfactory cortex through different materials to realize olfactory function.The sensor array used to sense external gas stimulation can be analyzed based on different recognition principles through different original signals such as optics,electricity,electrochemistry and bioelectricity.Furthermore,combined with pattern recognition and microarray technology,artificial nose can be highly integrated with biocompatible and other important properties to achieve in vitro application.The design principle and necessary components of artificial nose are introduced in this paper including sensing structure,recognition system and functional module.At the same time,the potential development prospects of molecular recognition technology,polymer-based materials and microarray integration in artificial nose are prospected.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金Supported in part by grants from the Russian Foundation for Basic Research,10-04-01599NIH RO1 DC000298
文摘We investigated the role of the main olfactory and accessory olfactory systems （MOS and AOS respectively） in the detection of androstenone. We used the following experimental approaches： behavioral, surgical removal of the vomeronasal organ （VNX） followed by histochemical verification and Fos immunohistochemistry. Using a Y-maze paradigm we estimated sensitivity of NZB/B1NJ and CBA/J mice to androstenone. CBA mice were 2,000-fold more sensitive to androstenone than NZB mice. VNX caused a 4-tol6-fold decrease in sensitivity to androstenone in highly-sensitive CBA mice, but did not affect thresholds in NZB mice. Results indicate the involvement of the MOS and AOS in the detection of androstenone. We observed a specific pattern of Fos-positive cells in the main olfactory bulb of CBA mice but not in NZB mice subsequent to exposure of mice to androstenone; the compound activated cells in the accessory olfactory bulb in both strains of mice, indicating the involvement of the vomeronasal organ. Patterns of Fos-positive cells in the vomeronasal organ were recorded subsequent to exposure to androstenone. Fos-positive receptor cells in the vomeronasal organ of CBA and NZB mice were different, in CBA mice Fos-positive cells were noted in both the basal and apical zones, however, in NZB mice activation was observed only in the apical zone [Current Zoology 56 （6）： 813-818, 2010].
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
基金supported by a grant from the Singer Biology Fund at the University of Florida。
文摘Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate with OR gene number,though debate exists on whether the number of total ORs,functional ORs,or the percentage of pseudogenes matters most.While olfaction has been poorly studied in most birds,Turkey Vultures(Cathartes aura)demonstrate keen olfactory ability,capable of foraging using smell alone.In contrast,Black Vultures(Coragyps atratus)have been thought to primarily use vision to locate food.Comparison of the OR genes in these two New World vultures presents an opportunity to examine the dynamics of OR evolution in related avian species that may differ in olfactory abilities.Using a PCR and cloning approach with degenerate primers,we sampled the OR subgenome in Turkey and Black Vultures,as well as Red-tailed Hawks(Buteo jamaicensis)and the distantly related Chicken(Gallus gallus),neither of which are thought to use olfaction extensively.Our results indicate that Turkey Vultures have many more OR genes than Red-tailed Hawks or chickens.Surprisingly,Black Vultures had an intermediate number of OR genes.The number of OR genes we estimated in the Turkey Vulture was much greater than previously reported in studies that used short-read sequencing.Additionally,we found that OR genes from New World vultures and Red-tailed Hawks form clades that were distinct from the clade that included most chicken OR genes,indicating that chickens share few OR orthologs with New World vultures or hawks.As previously observed in other animal groups,pseudogenes appeared throughout all clades and their percentage varied among taxa.These findings suggest the OR gene family is highly dynamic,changing rapidly over evolutionary time,and that taxa may have distinct suites of ORs in their genomes.
基金Supported by Hangzhou Medical and Health Technology Project,No.B20210443.
文摘BACKGROUND Congenital olfactory disorders(CODs)are rare but impactful conditions that impair the sense of smell from birth.These disorders can significantly affect a child’s appetite,nutrition,safety awareness,and overall quality of life.Despite their clinical importance,treatment options for CODs remain limited and largely ineffective,with no established therapies capable of restoring olfactory function in pediatric patients.Recent advances in regenerative medicine and stem cell therapy offer promising avenues for addressing sensory deficits.Nasal epithelial stem cells have emerged as a viable candidate for therapeutic intervention due to their accessibility and intrinsic ability to differentiate into olfactory sensory neurons.Preliminary studies suggest their potential in promoting the re-generation of the olfactory epithelium and functional recovery.However,long-term data on the efficacy and safety of such approaches in children are lacking.AIM To evaluate the long-term efficacy and safety of autologous nasal epithelial stem cell transplantation for the treatment of CODs in children.METHODS This prospective,single-center study enrolled 50 children aged 3-15 years with CODs.All patients underwent autologous nasal epithelial stem cell transplantation and were followed up for 3 years.The primary outcome measure was change in olfactory function,assessed using the Sniffin’Sticks test and the University of Pennsylvania Smell Identification Test-Children’s Version.Secondary outcomes included quality of life(measured by the Pediatric Quality of Life Inventory™and a custom olfaction-specific questionnaire),safety,endoscopic evaluation,and electro-olfactogram measurements.Data were analyzed using repeated measures analysis of variance,Friedman’s test,and multiple regression analysis.RESULTS The mean composite olfactory score increased from 8.3±4.7 at baseline to 52.6±18.9 at the 3-year follow-up(P<0.001).Significant improvement(≥50%increase in score)was observed in 60%of patients,with 24%showing moderate improvement.Quality of life scores improved significantly across all domains(P<0.001).No serious adverse events were reported.Minor complications occurred in 16%of patients,which resolved within 2 weeks.Endoscopic evaluation revealed normal-appearing olfactory epithelium in 84%of patients at 3 years,compared to 24%at baseline(P<0.001).Electro-olfactogram amplitudes increased from 0.11±0.08 mV to 0.67±0.31 mV(P<0.001).Age at intervention(β=0.31,P=0.02)and baseline residual olfactory function(β=0.45,P<0.001)were positively associated with treatment outcomes.CONCLUSION Autologous nasal epithelial stem cell transplantation demonstrates significant and sustained improvements in olfactory function and quality of life in children with CODs,with a favorable safety profile over a 3-year follow-up period.This approach represents a promising advancement in the treatment of pediatric sensory disorders.
