Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion cha...Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-in...c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.展开更多
This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore t...This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.展开更多
Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance protei...Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.展开更多
Spinal muscular atrophy （SMA） is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Thr...Spinal muscular atrophy （SMA） is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship： SMA1, SMA2, and SMA3. The survival of motor neuron （SMN） gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein （NAlP） gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction （PCR） combined with restriction fragment length polymorphism （RFLP） was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% （13/17） of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMNI exon 7 along with 24% （4/17） of SMA2 patients. Eleven out of 32 （34%） SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NA1P deletion. The findings of homozygous deletions ofexon 7 and/or exon 8 ofSMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion ofSMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMAI. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.展开更多
Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity o...Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.展开更多
Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathw...Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.展开更多
Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain isch...Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.展开更多
Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui（GV20） acupoint for 30 minute...Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui（GV20） acupoint for 30 minutes at 1 m A and 2/15 Hz for 5 consecutive days. A cerebral ischemia model was established by ligating the bilateral common carotid artery for 15 minutes. At 72 hours after injury, neuronal injury in the mouse hippocampus had lessened, and the number of terminal deoxynucleotide transferase-mediated d UTP nick-end labeling-positive cells reduced after electroacupuncture treatment. Moreover, expression of adenosine monophosphate-activated protein kinase α（AMPKα） and phosphorylated AMPKα was up-regulated. Intraperitoneal injection of the AMPK antagonist, compound C, suppressed this phenomenon. Our findings suggest that electroacupuncture preconditioning alleviates ischemic brain injury via AMPK activation.展开更多
BACKGROUND： Both c-Fos protein and nitricoxide synthase （NOS） have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to ...BACKGROUND： Both c-Fos protein and nitricoxide synthase （NOS） have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE： To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN： Randomized control experiment.SETTING ： Department of Histology and Embryology, Luzhou Medical College.MATERIALS ： Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University （batch number： 01062310）. METHODS ： This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ①Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8： 00 am next day. On the 15^th conceiving day, all conceiving rats were divided randomly into three groups： control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group： Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group： Rats were injected with the same volume of saline. Control group： Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance （ANOVA） followed by q test. MAIN OUTCOME MEASURES： ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS：① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group （76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35±6.67, P 〈 0.05）, but those in Angelica group were less than those in hypoxia group （51.70±9.82, 35.65±8.37, P 〈 0.05）. CONCLUSION： Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.展开更多
The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of se...The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of sex pheromone communication.The recognition of sex pheromones is vital for courtship and mating behaviors,and is mediated by various chemosensory-associated proteins.Among these,sensory neuron membrane protein(SNMP),a CD36-related protein,is suggested to play crucial roles in detecting sex pheromones.In this study,we employed transcriptomic and genomic data from A.lucorum and phylogenetic approaches,and identified four putative SNMP genes(AlucSNMP1a,AlucSNMP1b,AlucSNMP2a,and AlucSNMP2b)with full open reading frames.Expression analysis revealed the ubiquitous presence of AlucSNMP transcripts in multiple tissues,with only AlucSNMP1a exhibiting male-biased expression in the antennae,suggesting its potential role in male chemosensation.Functional analysis using the Xenopus oocyte expression system,coupled with two-electrode voltage clamp recording,demonstrated that the co-expression of AlucSNMP1a with specific pheromone receptors(PRs)and the Odorant receptor co-receptor(Orco)significantly enhanced electrophysiological responses to sex pheromones compared to the co-expression of PRs and Orco alone.Moreover,the results indicated that the presence of AlucSNMP1a not only affected the responsiveness to sex pheromones but also influenced the kinetics(activation and inactivation)of the induced signals.In contrast,the co-expression of AlucSNMP1b with AlucPR/Orco complexes had no impact on the inward currents induced by two pheromone compounds.An examination of the selective pressures on SNMP1 genes across 20 species indicated strong purifying selection,implying potential functional conservation in various insects.These findings highlight the crucial role of AlucSNMP1a in the response to sex pheromones.展开更多
Spinal muscular atrophy （SMA） is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and ...Spinal muscular atrophy （SMA） is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and trunk paralysis and muscular atrophy. Depending on the age of onset and maximum muscular function achieved, SMA is recognized as SMA1, SMA2, SMA3 or SMA4, and most patients have a deletion or truncation of the survival motor neuron 1 （SMN1） gene. In this report, we present a patient with a mild SMA phenotype, SMA3, and define his genetic abnormality. Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient. A 500 kb deletion in chromosome 5q13.2, including homozygous deletion of neuronal apoptosis inhibitory protein, and heterozygous deletion of occludin and B-double prime 1 was identified. This SMA region deletion did not involve SMN, indicating that SMN was likely to function normally. The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein, occludin and B-double prime 1 may be candidate genes for SMA3.展开更多
GIT1,a G-protein-coupled receptor kinase interacting protein,has been reported to be involved in neurite outgrowth.However,the neurobiological functions of the protein remain unclear.In this study,we found that GIT1 w...GIT1,a G-protein-coupled receptor kinase interacting protein,has been reported to be involved in neurite outgrowth.However,the neurobiological functions of the protein remain unclear.In this study,we found that GIT1 was highly expressed in the nervous system,and its expression was maintained throughout all stages of neuritogenesis in the brain.In primary cultured mouse hippocampal neurons from GIT1 knockout mice,there was a significant reduction in total neurite length per neuron,as well as in the average length of axon-like structures,which could not be prevented by nerve growth factor treatment.Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice.The GIT1 N terminal region,including the ADP ribosylation factor-GTPase activating protein domain,the ankyrin domains and the Spa2 homology domain,were sufficient to enhance axonal extension.Importantly,GIT1 bound to many tubulin proteins and microtubule-associated proteins,and it accelerated microtubule assembly in vitro.Collectively,our findings suggest that GIT1 promotes neurite outgrowth,at least partially by stimulating microtubule assembly.This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.展开更多
Sensory neuron membrane proteins(SNMPs),homologs of the human fatty acid transport protein CD36 family,are observed to play a significant role in chemoreception,especially in detecting sex pheromone in Drosophila and ...Sensory neuron membrane proteins(SNMPs),homologs of the human fatty acid transport protein CD36 family,are observed to play a significant role in chemoreception,especially in detecting sex pheromone in Drosophila and some lepidopteran species.In the current study,two full‐length SNMP transcripts,MmedSNMP1 and MmedSNMP2,were identified in the parasitoid Microplitis mediator(Hymenoptera:Braconidae).Quantitative real‐time polymerase chain reaction analysis showed that the expression of MmedSNMP1 was significantly higher in antennae than in other tissues of both sexes.In addition,the MmedSNMP1 transcript was increased dramatically in newly emerged adults and there were no significant differences between adults with or without mating and parasitic experiences.However,compared with MmedSNMP1,the expression of MmedSNMP2 was widely found in various tissues,significantly increased at half‐pigmented pupae stage and remained at a relatively constant level during the following developmental stages.It was found that MmedSNMP1 contained eight exons and seven introns,which was highly conserved compared with other insect species.In situ hybridization assay demonstrated that MmedSNMP1 transcript was distributed widely in antennal flagella.Among selected chemosensory genes(odorant binding protein,odorant receptor,and ionotropic receptor genes),MmedSNMP1 only partially overlapped with MmedORco in olfactory sensory neurons of antennae.Subsequent immunolocalization results further indicated that MmedSNMP1 was mainly expressed in sensilla placodea of antennae and possibly involved in perceiving plant volatiles and sex pheromones.These findings lay a foundation for further investigating the roles of SNMPs in the chemosensation of parasitoids.展开更多
Sensory neuron membrane proteins （SNMPs）, which are located on the dendritic membrane of olfactory sensory neurons （OSNs）, are proposed to be associated with odor reception in insects. Recent studies have demonstr...Sensory neuron membrane proteins （SNMPs）, which are located on the dendritic membrane of olfactory sensory neurons （OSNs）, are proposed to be associated with odor reception in insects. Recent studies have demonstrated that SNMP1 is essential for electrophysiological responses of OSNs to the sex pheromone, cis-vaccenyl acetate （cVA） in Drosophila melanogaster. To investigate the function ofLepidoptera SNMPs, we cloned two SNMP genes, SlituSNMP1 and SltiuSNMP2, from Spodoptera litura （Lepidoptera： Noctuidae）. Sequence alignment and phylogenetic analysis showed that both genes bear the general characteristics of SNMPs, including six conserved cysteine residues and two transmembrane domains. Further expression profile experiments showed that SIituSNMP1 is mainly expressed in the antenna, while SlituSNMP2 is broadly expressed in various tissues. By in situ hybridization experiments, it was found that SlituSNMP1 expressing cells are surrounded by the SlituSNMP2 expressing cells in the pheromone sensitive sensilla, suggesting different fimctions ＆the two SNMPs in insect olfaction.展开更多
Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response ...Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.展开更多
文摘Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金supported by the Henan Province Education Department Key Project of Science and Technology Research in China,No.12A350006
文摘c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.
文摘This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.
基金supported by Shenzhen University General Hospital Scientific Research Project,No.SUGH2019QD002Shenzhen Science and Technology Development Foundation,No.20220810173216001(both to ZS).
文摘Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.
基金Project supported by the National Natural Science Foundation of China (No. J0710043)the Natural Science Foundation of Zheji-ang Province (No. 2007C33049), China
文摘Spinal muscular atrophy （SMA） is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship： SMA1, SMA2, and SMA3. The survival of motor neuron （SMN） gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein （NAlP） gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction （PCR） combined with restriction fragment length polymorphism （RFLP） was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% （13/17） of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMNI exon 7 along with 24% （4/17） of SMA2 patients. Eleven out of 32 （34%） SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NA1P deletion. The findings of homozygous deletions ofexon 7 and/or exon 8 ofSMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion ofSMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMAI. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.
基金supported by the Guangdong Provincial Department of Science and Technology in China,No.2016A020225007
文摘Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HQ065a grant from the Medical Science and Technology Development Project of Shandong Province of China,No.2015WS0445
文摘Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.
文摘Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.
基金supported by the National Natural Science Foundation of China,No.81273821
文摘Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui（GV20） acupoint for 30 minutes at 1 m A and 2/15 Hz for 5 consecutive days. A cerebral ischemia model was established by ligating the bilateral common carotid artery for 15 minutes. At 72 hours after injury, neuronal injury in the mouse hippocampus had lessened, and the number of terminal deoxynucleotide transferase-mediated d UTP nick-end labeling-positive cells reduced after electroacupuncture treatment. Moreover, expression of adenosine monophosphate-activated protein kinase α（AMPKα） and phosphorylated AMPKα was up-regulated. Intraperitoneal injection of the AMPK antagonist, compound C, suppressed this phenomenon. Our findings suggest that electroacupuncture preconditioning alleviates ischemic brain injury via AMPK activation.
基金the Natural Science Foundation of Sichuan Educational Bureau, No. Chuanjiaoji (2001) 149-01LA40
文摘BACKGROUND： Both c-Fos protein and nitricoxide synthase （NOS） have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE： To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN： Randomized control experiment.SETTING ： Department of Histology and Embryology, Luzhou Medical College.MATERIALS ： Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University （batch number： 01062310）. METHODS ： This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ①Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8： 00 am next day. On the 15^th conceiving day, all conceiving rats were divided randomly into three groups： control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group： Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group： Rats were injected with the same volume of saline. Control group： Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance （ANOVA） followed by q test. MAIN OUTCOME MEASURES： ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS：① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group （76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35±6.67, P 〈 0.05）, but those in Angelica group were less than those in hypoxia group （51.70±9.82, 35.65±8.37, P 〈 0.05）. CONCLUSION： Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.
基金supported by the National Natural Science Foundation of China(32150410366,31972338,and32372639)the earmarked fund for China Agriculture Research System(CARS-02-26)+1 种基金the National Key Research and Development Program of China(2021YFD1400700)the Special Grant of China Postdoctoral Science Foundation(2022T150712)。
文摘The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of sex pheromone communication.The recognition of sex pheromones is vital for courtship and mating behaviors,and is mediated by various chemosensory-associated proteins.Among these,sensory neuron membrane protein(SNMP),a CD36-related protein,is suggested to play crucial roles in detecting sex pheromones.In this study,we employed transcriptomic and genomic data from A.lucorum and phylogenetic approaches,and identified four putative SNMP genes(AlucSNMP1a,AlucSNMP1b,AlucSNMP2a,and AlucSNMP2b)with full open reading frames.Expression analysis revealed the ubiquitous presence of AlucSNMP transcripts in multiple tissues,with only AlucSNMP1a exhibiting male-biased expression in the antennae,suggesting its potential role in male chemosensation.Functional analysis using the Xenopus oocyte expression system,coupled with two-electrode voltage clamp recording,demonstrated that the co-expression of AlucSNMP1a with specific pheromone receptors(PRs)and the Odorant receptor co-receptor(Orco)significantly enhanced electrophysiological responses to sex pheromones compared to the co-expression of PRs and Orco alone.Moreover,the results indicated that the presence of AlucSNMP1a not only affected the responsiveness to sex pheromones but also influenced the kinetics(activation and inactivation)of the induced signals.In contrast,the co-expression of AlucSNMP1b with AlucPR/Orco complexes had no impact on the inward currents induced by two pheromone compounds.An examination of the selective pressures on SNMP1 genes across 20 species indicated strong purifying selection,implying potential functional conservation in various insects.These findings highlight the crucial role of AlucSNMP1a in the response to sex pheromones.
基金the Foundation of Science and Technology Department of Zhejiang Province,China,No. 2007C33049Fund for Fostering Talents in Basic Science of the National Natural Science Foundation of China,No. J0710043
文摘Spinal muscular atrophy （SMA） is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and trunk paralysis and muscular atrophy. Depending on the age of onset and maximum muscular function achieved, SMA is recognized as SMA1, SMA2, SMA3 or SMA4, and most patients have a deletion or truncation of the survival motor neuron 1 （SMN1） gene. In this report, we present a patient with a mild SMA phenotype, SMA3, and define his genetic abnormality. Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient. A 500 kb deletion in chromosome 5q13.2, including homozygous deletion of neuronal apoptosis inhibitory protein, and heterozygous deletion of occludin and B-double prime 1 was identified. This SMA region deletion did not involve SMN, indicating that SMN was likely to function normally. The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein, occludin and B-double prime 1 may be candidate genes for SMA3.
基金supported by the grants to HLS from the National Natural Science Foundation of China(81371507)Medicine and Engineering Cross-talking Funds of Shanghai Jiao Tong University(YG2013MS40)+8 种基金Science and Technology Projects of Shanghai Jiao Tong University Medical School(13XJ10016)the National Basic Research Program of China(973 Program2013CB945600)by the grants to WQG from the Chinese Ministry of Science and Technology(2012CB966800 and 2013CB945600)the National Natural Science Foundation of China(81130038 and 81372189)the Science and Technology Commission of Shanghai Municipality(Pujiang Program)the Shanghai Health Bureau Key Disciplines and Specialties Foundationthe Shanghai Education Committee Key Discipline and Specialties Foundation(J50208)KC Wong Foundation
文摘GIT1,a G-protein-coupled receptor kinase interacting protein,has been reported to be involved in neurite outgrowth.However,the neurobiological functions of the protein remain unclear.In this study,we found that GIT1 was highly expressed in the nervous system,and its expression was maintained throughout all stages of neuritogenesis in the brain.In primary cultured mouse hippocampal neurons from GIT1 knockout mice,there was a significant reduction in total neurite length per neuron,as well as in the average length of axon-like structures,which could not be prevented by nerve growth factor treatment.Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice.The GIT1 N terminal region,including the ADP ribosylation factor-GTPase activating protein domain,the ankyrin domains and the Spa2 homology domain,were sufficient to enhance axonal extension.Importantly,GIT1 bound to many tubulin proteins and microtubule-associated proteins,and it accelerated microtubule assembly in vitro.Collectively,our findings suggest that GIT1 promotes neurite outgrowth,at least partially by stimulating microtubule assembly.This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.
基金This work was supported by the National Natural Science Foundation of China(31471778,31672038,31621064 and 31772176).
文摘Sensory neuron membrane proteins(SNMPs),homologs of the human fatty acid transport protein CD36 family,are observed to play a significant role in chemoreception,especially in detecting sex pheromone in Drosophila and some lepidopteran species.In the current study,two full‐length SNMP transcripts,MmedSNMP1 and MmedSNMP2,were identified in the parasitoid Microplitis mediator(Hymenoptera:Braconidae).Quantitative real‐time polymerase chain reaction analysis showed that the expression of MmedSNMP1 was significantly higher in antennae than in other tissues of both sexes.In addition,the MmedSNMP1 transcript was increased dramatically in newly emerged adults and there were no significant differences between adults with or without mating and parasitic experiences.However,compared with MmedSNMP1,the expression of MmedSNMP2 was widely found in various tissues,significantly increased at half‐pigmented pupae stage and remained at a relatively constant level during the following developmental stages.It was found that MmedSNMP1 contained eight exons and seven introns,which was highly conserved compared with other insect species.In situ hybridization assay demonstrated that MmedSNMP1 transcript was distributed widely in antennal flagella.Among selected chemosensory genes(odorant binding protein,odorant receptor,and ionotropic receptor genes),MmedSNMP1 only partially overlapped with MmedORco in olfactory sensory neurons of antennae.Subsequent immunolocalization results further indicated that MmedSNMP1 was mainly expressed in sensilla placodea of antennae and possibly involved in perceiving plant volatiles and sex pheromones.These findings lay a foundation for further investigating the roles of SNMPs in the chemosensation of parasitoids.
基金We would like to thank Li-Yan Yang for insect rearing, Shu-Wei Yan and Meng-Bo Guo for technical assistance in the qRT-PCR and in situ hybridization. This work was supported by the National Basic Research Program of China （Grant No. 2012CB114104）, the National Natural Science Foundation of China （Grant No. 31230062 and 31071752） and Beijing Natural Science Foundation （6132028）.
文摘Sensory neuron membrane proteins （SNMPs）, which are located on the dendritic membrane of olfactory sensory neurons （OSNs）, are proposed to be associated with odor reception in insects. Recent studies have demonstrated that SNMP1 is essential for electrophysiological responses of OSNs to the sex pheromone, cis-vaccenyl acetate （cVA） in Drosophila melanogaster. To investigate the function ofLepidoptera SNMPs, we cloned two SNMP genes, SlituSNMP1 and SltiuSNMP2, from Spodoptera litura （Lepidoptera： Noctuidae）. Sequence alignment and phylogenetic analysis showed that both genes bear the general characteristics of SNMPs, including six conserved cysteine residues and two transmembrane domains. Further expression profile experiments showed that SIituSNMP1 is mainly expressed in the antenna, while SlituSNMP2 is broadly expressed in various tissues. By in situ hybridization experiments, it was found that SlituSNMP1 expressing cells are surrounded by the SlituSNMP2 expressing cells in the pheromone sensitive sensilla, suggesting different fimctions ＆the two SNMPs in insect olfaction.
文摘Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.
