Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairmen...Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can...Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can respond immediately to the threat.Therefore,when an animal detects a threat through its visual system,it must quickly direct its gaze and attention toward the source of danger,assess the threat level,and take appropriate action.展开更多
Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental pati...Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.展开更多
DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plast...DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].展开更多
The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatal...The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatalytic conversion of N_(2) to NH_(3) using solar energy is an eco-friendly method,it has the limitation of low quantum yield.Recently,2D Bi-based photocatalysts which exhibit higher visible light absorption than TiO_(2) and higher stability than MXene have been an active research topic,and their performance can be enhanced through improved visible light absorption properties by incorporating plasmonic gold nanoparticles while nitrogen adsorption could be enhanced through oxygen vacancy(OV)processes.In the present study,we explore the application of 2D nanosized Bi_(2)O_(3–x) and gold nanoparticles for visible light photo generation of NH_(3).HRTEM and XPS reveal that the formation of AuNP and nano-sized Bi_(2)O_(3–x) in AuNP/Bi_(2)O_(3–x) heterozygote structure promotes the charge carrier mobility and charge transport at the interface,resulting in a 2.6-fold increase in the photocatalytic activity compared to micro-sized Bi_(2)O_(3–x) with AuNP.The improved photocatalytic performance can be ascribed to significant enhancement of visible light absorption by plasmonic nanoparticles,fast charge transport and mobility(due to sheet morphology)and the N_(2) activation by OV in AuNP/Bi_(2)O_(3–x) heterozygote.Through a systematic experimental investigation involving catalysts,concentration,pH,and scavengers,the highest photocatalytic performance was achieved with the heterozygote structures of AuNP/n-Bi_(2)O_(3–x) under optimized conditions,yielding 432.5μmol gcat^(-1) h^(-1) of NH_(3).展开更多
Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used si...Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.展开更多
Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained atten...Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained attention,with a particular focus on how daily step count affects various sleep metrics.展开更多
Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associa...Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associated with several diseases,such as obstructive sleep apnea(OSA) and sudden infant death syndrome.OS A is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states.Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA.However,the presynaptic partners governing the activity of HMNs remain to be elucidated.In the present study,we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice.We identified 53 nuclei targeting HMNs from six brain regions:the amygdala,hypothalamus,midbrain,pons,medulla,and cerebellum.We discovered that GAB Aergic neurons in the central amygdaloid nucleus,as well as calretinin neurons in the parasubthalamic nucleus,sent monosynaptic projections to HMNs.In addition,HMNs received direct inputs from several regions associated with respiration,such as the preBotzinger complex,parabrachial nucleus,nucleus of the solitary tract,and hypothalamus.Some regions engaged in sleep-wake regulation(the parafacial zone,parabrachial nucleus,ventral medulla,sublaterodorsal tegmental nucleus,dorsal raphe nucleus,periaqueductal gray,and hypothalamus) also provided primary inputs to HMNs.These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.展开更多
The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain function...The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain functions,the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal.Recent studies utilized one single long run for task trials of the same condition,the so-called continuous design,to investigate functional connectivity based on task functional magnetic resonance imaging.Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment,which has been examined for working memory,sensory,motor,and semantic task experiments in previous research.But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks.This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks,by using repeated-measures analysis of variance.Across 50 young healthy adults,behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load.Imaging results revealed that the cingulo-opercular,fronto-parietal,and default model networks were associated with not only task activation,but significant main effects of design and load as well as their interaction on intra-and inter-network functional connectivity and global network topology.Moreover,a significant behavior-brain association was identified for the continuous design.This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.展开更多
OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubme...OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of ＂brain natriuretic pepfide （BNP）, central nervous system, subarachnoid hemorrhage （SAH）, brain edema, epilepsy＂. Other articles were searched in China Hospital Knowledge Database （CHKD） by concrete name of journals and title of articles. STUDY SELECTION： The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION： Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS： At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without - outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION： As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.展开更多
The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1]...The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1].As one of the key components of the NSC niche,astrocytes are vital in regulating the processes underlying brain development such as neuro-/gliogenesis,angiogenesis,axonal outgrowth,synaptogenesis,and synaptic pruning[2].Chemical and electrical signals mediated by adhesion molecules,the extracellular matrix,paracrine secretion.展开更多
The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. D...The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis.This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.展开更多
Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similari...Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.展开更多
Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we i...Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.展开更多
The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other ...The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other brain regions,revealing the crucial role of this area in integrating sensory,emotional,and cognitive information.The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain.We summarize its role in interoceptive and exteroceptive sensory processing,illustrating insular function as a bridge connecting internal and external experiences.Drawing on recent research,we delineate the insular involvement in emotional processes,highlighting its implications in psychiatric conditions,such as anxiety,depression,and addiction.We further discuss the insular contributions to cognition,focusing on its significant roles in time perception and decision-making.Collectively,the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes.Through this review,we hope to highlight the importance of the insula as an interface between sensation,emotion,and cognition,and to inspire further research into this fascinating brain region.展开更多
Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the pr...Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.展开更多
基金supported by the University of Macao(MYRG2022-00054-FHS and MYRGGRG2023-00038-FHS-UMDF)the Macao Science and Technology Development Fund(FDCT0048/2021/AGJ and FDCT0020/2019/AMJ)Natural Science Foundation of Guangdong Province(EF017/FHS-YZ/2021/GDSTC).
文摘Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金supported by the National Natural Science Foundation of China(32471055 and 82171090)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12).
文摘Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can respond immediately to the threat.Therefore,when an animal detects a threat through its visual system,it must quickly direct its gaze and attention toward the source of danger,assess the threat level,and take appropriate action.
基金supported by the National Research Foundation(NRF)of Korea(grant number:RS-2022-NR072217 to P.RL,RS-2021-NR059709,RS-2023-00264409,and RS-2024-00441103)funded by the Korean government(MSIT).
文摘Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
基金supported by the National Natural Science Foundation of China(T2394531)the National Key R&D Program of China(2024YFF1206500)+1 种基金the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and the Shanghai Center for Brain Science and Brain-Inspired Technology,China.
文摘DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].
基金Financial support for this work by the National Research Foundation of Korea(2022R1F1A1074682,2022R1A4A1031687)Korea University,and the KU-KIST Research Fund.
文摘The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatalytic conversion of N_(2) to NH_(3) using solar energy is an eco-friendly method,it has the limitation of low quantum yield.Recently,2D Bi-based photocatalysts which exhibit higher visible light absorption than TiO_(2) and higher stability than MXene have been an active research topic,and their performance can be enhanced through improved visible light absorption properties by incorporating plasmonic gold nanoparticles while nitrogen adsorption could be enhanced through oxygen vacancy(OV)processes.In the present study,we explore the application of 2D nanosized Bi_(2)O_(3–x) and gold nanoparticles for visible light photo generation of NH_(3).HRTEM and XPS reveal that the formation of AuNP and nano-sized Bi_(2)O_(3–x) in AuNP/Bi_(2)O_(3–x) heterozygote structure promotes the charge carrier mobility and charge transport at the interface,resulting in a 2.6-fold increase in the photocatalytic activity compared to micro-sized Bi_(2)O_(3–x) with AuNP.The improved photocatalytic performance can be ascribed to significant enhancement of visible light absorption by plasmonic nanoparticles,fast charge transport and mobility(due to sheet morphology)and the N_(2) activation by OV in AuNP/Bi_(2)O_(3–x) heterozygote.Through a systematic experimental investigation involving catalysts,concentration,pH,and scavengers,the highest photocatalytic performance was achieved with the heterozygote structures of AuNP/n-Bi_(2)O_(3–x) under optimized conditions,yielding 432.5μmol gcat^(-1) h^(-1) of NH_(3).
基金supported by the Institute for Basic Science (IBS-R022-D1)Global Learning&Academic Research Institution for Master’s/Ph D students and Post-Doc Program of the National Research Foundation of Korea Grant funded by the Ministry of Education (RS-2023-00301938)+1 种基金National Research Foundation of Korea Grant funded by the Korean government (RS-2024-00406152,MSIT)Additional financial support was provided by the 2024 Post-Doc Development Program of Pusan National University,Korea Medical Institute,and KREONET。
文摘Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.
文摘Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained attention,with a particular focus on how daily step count affects various sleep metrics.
基金supported by the National Natural Science Foundation of China (31530035,81420108015, 31671099,31871072,81570081,81770083 and 31971110)the National Basic Research Development Program of China (2015CB856401)+2 种基金the Program for Shanghai Outstanding Academic Leaders (to ZLH)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)the National Key Research and Development Program of China (2018YFC1313600)。
文摘Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associated with several diseases,such as obstructive sleep apnea(OSA) and sudden infant death syndrome.OS A is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states.Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA.However,the presynaptic partners governing the activity of HMNs remain to be elucidated.In the present study,we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice.We identified 53 nuclei targeting HMNs from six brain regions:the amygdala,hypothalamus,midbrain,pons,medulla,and cerebellum.We discovered that GAB Aergic neurons in the central amygdaloid nucleus,as well as calretinin neurons in the parasubthalamic nucleus,sent monosynaptic projections to HMNs.In addition,HMNs received direct inputs from several regions associated with respiration,such as the preBotzinger complex,parabrachial nucleus,nucleus of the solitary tract,and hypothalamus.Some regions engaged in sleep-wake regulation(the parafacial zone,parabrachial nucleus,ventral medulla,sublaterodorsal tegmental nucleus,dorsal raphe nucleus,periaqueductal gray,and hypothalamus) also provided primary inputs to HMNs.These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.
基金supported by the National Natural Science Foundation of China(62071109 and 61871420)the Provincial Natural Science Foundation of Sichuan(2022NSFSC0504).
文摘The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain functions,the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal.Recent studies utilized one single long run for task trials of the same condition,the so-called continuous design,to investigate functional connectivity based on task functional magnetic resonance imaging.Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment,which has been examined for working memory,sensory,motor,and semantic task experiments in previous research.But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks.This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks,by using repeated-measures analysis of variance.Across 50 young healthy adults,behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load.Imaging results revealed that the cingulo-opercular,fronto-parietal,and default model networks were associated with not only task activation,but significant main effects of design and load as well as their interaction on intra-and inter-network functional connectivity and global network topology.Moreover,a significant behavior-brain association was identified for the continuous design.This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.
基金the National Natural Science Foundation of China, No. 30371451
文摘OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of ＂brain natriuretic pepfide （BNP）, central nervous system, subarachnoid hemorrhage （SAH）, brain edema, epilepsy＂. Other articles were searched in China Hospital Knowledge Database （CHKD） by concrete name of journals and title of articles. STUDY SELECTION： The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION： Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS： At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without - outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION： As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.
基金AcknowledgementsThis research highlight was supported by STI 2030-Major Projects(2021ZD0203201),the National Natural Science Foundation of China(81971034,32271047),The Innovative Research Team of High-level Local Universities in Shanghai,Natural Science Foundation of Shanghai(22ZR1413800),The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01),ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology,Lingang Laboratory(LGQS-202203-12),Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTDC-202008),and Shanghai Style of TCM for Inheritance and Innovation Team from Shanghai Municipal Health Commission(2021LPTD-007),Shanghai Artificial Intelligence Innovation and Development Project-Intelligent Dermatology Clinic Based on Modern TCM Diagnostic Technology,No.2020-RGZN-02038.
文摘The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1].As one of the key components of the NSC niche,astrocytes are vital in regulating the processes underlying brain development such as neuro-/gliogenesis,angiogenesis,axonal outgrowth,synaptogenesis,and synaptic pruning[2].Chemical and electrical signals mediated by adhesion molecules,the extracellular matrix,paracrine secretion.
基金supported by the National Natural Science Foundation of China (No. 81973639 and 81573712)the Innovative Research Team of High-level Local Universities in ShanghaiShanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function (No. 21DZ2271800)。
文摘The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis.This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.
基金supported by the Zhongshan-Fudan Joint Innovation Center,Zhongshan,Guangdong Province,China(528437)the National Natural Science Foundation of China(82271258,82271248,82204830,81971056)+1 种基金Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.
基金supported by the National Natural Science Foundation of China,Nos.81871024 (to HN),82301957 (to XW),82001382 (to LL),62127810 (to HN)the Natural Science Foundation of Jiangsu Province of China,No.SBK2020040785 (to LL)。
文摘Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.
基金supported by grants from the National Natural Science Foundation of China(32371060 and 32271065)the Lingang Laboratory(LG-QS-202203-06 and LG-QS-202203-02)the Chinese Academy of Sciences,and Benyuan Charity Foundation.
文摘The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other brain regions,revealing the crucial role of this area in integrating sensory,emotional,and cognitive information.The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain.We summarize its role in interoceptive and exteroceptive sensory processing,illustrating insular function as a bridge connecting internal and external experiences.Drawing on recent research,we delineate the insular involvement in emotional processes,highlighting its implications in psychiatric conditions,such as anxiety,depression,and addiction.We further discuss the insular contributions to cognition,focusing on its significant roles in time perception and decision-making.Collectively,the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes.Through this review,we hope to highlight the importance of the insula as an interface between sensation,emotion,and cognition,and to inspire further research into this fascinating brain region.
基金supported by the STI 2030-Major Projects 2022ZD0208500(to DY)the National Natural Science Foundation of China,Nos.82072011(to YX),82121003(to DY),82271120(to YS)+2 种基金Sichuan Science and Technology Program,No.2022ZYD0066(to YS)a grant from Chinese Academy of Medical Science,No.2019-12M-5-032(to YS)the Fundamental Research Funds for the Central Universities,No.ZYGX2021YGLH219(to KC)。
文摘Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.
