Manipulating the expression of synaptic plasticity of neuromorphic devices provides fascinating opportunities to develop hardware platforms for artifi-cial intelligence.However,great efforts have been devoted to explo...Manipulating the expression of synaptic plasticity of neuromorphic devices provides fascinating opportunities to develop hardware platforms for artifi-cial intelligence.However,great efforts have been devoted to exploring biomimetic mechanisms of plasticity simulation in the last few years.Recent progress in various plasticity modulation techniques has pushed the research of synaptic electronics from static plasticity simulation to dynamic plasticity modulation,improving the accuracy of neuromorphic computing and providing strategies for implementing neuromorphic sensing functions.Herein,several fascinating strategies for synap-tic plasticity modulation through chemical techniques,device structure design,and physical signal sensing are reviewed.For chemical techniques,the underly-ing mechanisms for the modification of functional materials were clarified and its effect on the expression of synaptic plasticity was also highlighted.Based on device structure design,the reconfigurable operation of neuromorphic devices was well demonstrated to achieve programmable neuromorphic functions.Besides,integrating the sensory units with neuromorphic processing circuits paved a new way to achieve human-like intelligent perception under the modulation of physical signals such as light,strain,and temperature.Finally,considering that the relevant technology is still in the basic exploration stage,some prospects or development suggestions are put forward to promote the development of neuromorphic devices.展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheime...Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.展开更多
The occurrence of high temperature(HT)in crop production is becoming more frequent and unpredictable with global warming,severely threatening food security.The state of an organ’s growth and development is largely de...The occurrence of high temperature(HT)in crop production is becoming more frequent and unpredictable with global warming,severely threatening food security.The state of an organ’s growth and development is largely determined by the temperature conditions it is exposed to over time.Maize is the main cereal crop,and its stem growth and plant architecture are closely related to lodging resistance,and especially sensitive to temperature.However,systematic research on the timing effect of HT on the sequentially developing internode and stem is currently lacking.To identify the timing effect of HT on the morphology and plasticity of the stem in maize,two hybrids(Zhengdan 958(ZD958),Xianyu 335(XY335))characterized by distinct morphological traits in the stem were exposed to a 7-day HT treatment from the V6 to V17 stages(Vn presents the vegetative stage with n leaves fully expanded)in 2019-2020.The results demonstrated that exposure to HT during V6-V12 accelerated the rapid elongation of stems.For instance,HT occurring at V7 and V12 specifically promoted the lengths and weights of the 3rd-5th and 9th-11th internodes,respectively.Meanwhile,HT slowed the growth of internodes adjacent to the promoted internodes.Interestingly,compared with control,the plant height was significantly increased soon after HT treatment,but the promotion effect became narrower at the subsequent flowering stage,demonstrating a self-adjusting mechanism in the maize plant in response to HT.Importantly,HT altered the plant architectures,including a rising of the ear position and increase in the ear position coefficient.XY335 exhibited greater sensitivity in stem development than ZD958 under HT treatment.These findings improve our systematic understanding of the plasticity of internode and plant architecture in response to the timing of HT exposure.展开更多
Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize ...Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative therapies.The term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical neurosciences.Indeed,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.展开更多
Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane...Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.Myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.展开更多
Anelasticity, as an intrinsic property of amorphous solids, plays a significant role in understanding their relaxation and deformation mechanism. However, due to the lack of long-range order in amorphous solids, the s...Anelasticity, as an intrinsic property of amorphous solids, plays a significant role in understanding their relaxation and deformation mechanism. However, due to the lack of long-range order in amorphous solids, the structural origin of anelasticity and its distinction from plasticity remain elusive. In this work, using frozen matrix method, we study the transition from anelasticity to plasticity in a two-dimensional model glass. Three distinct mechanical behaviors, namely,elasticity, anelasticity, and plasticity, are identified with control parameters in the amorphous solid. Through the study of finite size effects on these mechanical behaviors, it is revealed that anelasticity can be distinguished from plasticity.Anelasticity serves as an intrinsic bridge connecting the elasticity and plasticity of amorphous solids. Additionally, it is observed that anelastic events are localized, while plastic events are subextensive. The transition from anelasticity to plasticity is found to resemble the entanglement of long-range interactions between element excitations. This study sheds light on the fundamental nature of anelasticity as a key property of element excitations in amorphous solids.展开更多
Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environme...Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific functions.Notably,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous system.During development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.展开更多
Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Over...Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Overall,different types of plasticity,including stem cell-driven genesis of new neurons(adult neurogenesis),cells in arrested maturation(dormant neurons),neuro-glial and synaptic plasticity,can coexist and contribute to grant plastic changes in the brain,from a cellular to system level(Benedetti and Couillard-Despres,2022;Bonfanti et al.,2023).展开更多
Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences ...Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticity might represent a potential neurophysiological marker for language function.展开更多
The superplastic behavior and associated deformation mechanisms of a fine-grained Mg-10.1 Li-0.8Al-0.6Zn alloy(LAZ1011)with a grain size of 3.2μm,primarily composed of the BCCβphase and a small amount of the HCPαph...The superplastic behavior and associated deformation mechanisms of a fine-grained Mg-10.1 Li-0.8Al-0.6Zn alloy(LAZ1011)with a grain size of 3.2μm,primarily composed of the BCCβphase and a small amount of the HCPαphase,were examined in a temperature range of 473 K to 623 K.The microstructural refinement of this alloy was achieved by employing high-ratio differential speed rolling.The best superplasticity was achieved at 523 K and at strain rates of 10^(-4)-5×10^(-4)s^(-1),where tensile elongations of 550±600%were obtained.During the heating and holding stage of the tensile samples prior to tensile loading,a significant increase in grain size was observed at temperatures above 573 K.Therefore,it was important to consider this effect when analyzing and understanding the superplastic deformation behavior and mechanisms.In the investigated strain rate range,the superplastic flow at low strain rates was governed by lattice diffusion-controlled grain boundary sliding,while at high strain rates,lattice diffusion-controlled dislocation climb creep was the rate-controlling deformation mechanism.It was concluded that solute drag creep is unlikely to occur.During the late stages of deformation at 523 K,it was observed that grain boundary sliding led to the agglomeration of theαphase,resulting in significant strain hardening.Deformation mechanism maps were constructed forβ-Mg-Li alloys in the form of 2D and 3D formats as a function of strain rate,stress,temperature,and grain size,using the constitutive equations for various deformation mechanisms derived based on the data of the current tests.展开更多
Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic ...Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.展开更多
Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalitie...Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalities for reducing glutamate accumulation.However,further research is needed to investigate the dynamic changes in and molecular mechanisms of glutamate transport and the effects of glutamate transport on synapses.The aim of this study was to investigate the regulatory mechanisms underlying Notch pathway mediation of glutamate transport and synaptic plasticity.In this study,Yorkshire neonatal pigs(male,age 3 days,weight 1.0–1.5 kg,n=48)were randomly divided into control(sham surgery group)and five hypoxic ischemia subgroups,according to different recovery time,which were then further subdivided into subgroups treated with dimethyl sulfoxide or a Notch pathway inhibitor(N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester).Once the model was established,immunohistochemistry,immunofluorescence staining,and western blot analyses of Notch pathway-related proteins,synaptophysin,and glutamate transporter were performed.Moreover,synapse microstructure was observed by transmission electron microscopy.At the early stage(6–12 hours after hypoxic ischemia)of hypoxic ischemic injury,expression of glutamate transporter excitatory amino acid transporter-2 and synaptophysin was downregulated,the number of synaptic vesicles was reduced,and synaptic swelling was observed;at 12–24 hours after hypoxic ischemia,the Notch pathway was activated,excitatory amino acid transporter-2 and synaptophysin expression was increased,and the number of synaptic vesicles was slightly increased.Excitatory amino acid transporter-2 and synaptophysin expression decreased after treatment with the Notch pathway inhibitor.This suggests that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin.展开更多
The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully d...The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled.To control cognitive function and behavior,the two systems are engaged in a subtle interacting act.In this scenario,a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging.Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes.In this dynamic equilibrium,synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro-and anti-inflammatory molecules in the central nervous system microenvironment.展开更多
Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,...Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.展开更多
Cave animals are an excellent model system for studying adaptive evolution.At present,however,little is known about the mechanisms that enable surface colonizers to survive in the challenging environment of caves.One ...Cave animals are an excellent model system for studying adaptive evolution.At present,however,little is known about the mechanisms that enable surface colonizers to survive in the challenging environment of caves.One possibility is that these species have the necessary genetic background to respond with plastic changes to the pressures of underground habitats.To gain insight into this process,we conducted a comparative study with the fish species Telestes karsticus,which occurs in a hydrological system consisting of an interconnected stream and a cave.Results showed that T.karsticus resided year-round and spawned in Sušik cave,making it the first known cavefish in the Dinaric Karst.Cave and surface populations differed in morphological and physiological characteristics,as well as in patterns of gene expression without any evidence of genetic divergence.To test whether observed trait differences were plastic or genetic,we placed adult fish from both populations under light/dark or constant dark conditions.Common laboratory conditions erased all morphometric differences between the two morphs,suggesting phenotypic plasticity is driving the divergence of shape and size in wild fish.Lighter pigmentation and increased fat deposition exhibited by cave individuals were also observed in surface fish kept in the dark in the laboratory.Our study also revealed that specialized cave traits were not solely attributed to developmental plasticity,but also arose from adult responses,including acclimatization.Thus,we conclude that T.karsticus can adapt to cave conditions,with phenotypic plasticity playing an important role in the process of cave colonization.展开更多
Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is wide...Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.展开更多
The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specializ...The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specialized molecular machinery is strategically placed to release and receive neurotransmitters and to generate and extinguish calcium(Ca^(2+))signals.These synaptic molecular components are highly dynamic and they influence each other to confer structural and functional adaptability(plasticity)to neuronal communication(Biederer et al.,2017).展开更多
基金financial support from the National Natural Science Foundation of China(Nos.62104017 and 52072204)Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘Manipulating the expression of synaptic plasticity of neuromorphic devices provides fascinating opportunities to develop hardware platforms for artifi-cial intelligence.However,great efforts have been devoted to exploring biomimetic mechanisms of plasticity simulation in the last few years.Recent progress in various plasticity modulation techniques has pushed the research of synaptic electronics from static plasticity simulation to dynamic plasticity modulation,improving the accuracy of neuromorphic computing and providing strategies for implementing neuromorphic sensing functions.Herein,several fascinating strategies for synap-tic plasticity modulation through chemical techniques,device structure design,and physical signal sensing are reviewed.For chemical techniques,the underly-ing mechanisms for the modification of functional materials were clarified and its effect on the expression of synaptic plasticity was also highlighted.Based on device structure design,the reconfigurable operation of neuromorphic devices was well demonstrated to achieve programmable neuromorphic functions.Besides,integrating the sensory units with neuromorphic processing circuits paved a new way to achieve human-like intelligent perception under the modulation of physical signals such as light,strain,and temperature.Finally,considering that the relevant technology is still in the basic exploration stage,some prospects or development suggestions are put forward to promote the development of neuromorphic devices.
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
基金supported by the National Natural Science Foundation of China,No.82074533(to LZ).
文摘Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.
基金This work was supported by the earmarked fund for China Agriculture Research System(CARS-02-16).
文摘The occurrence of high temperature(HT)in crop production is becoming more frequent and unpredictable with global warming,severely threatening food security.The state of an organ’s growth and development is largely determined by the temperature conditions it is exposed to over time.Maize is the main cereal crop,and its stem growth and plant architecture are closely related to lodging resistance,and especially sensitive to temperature.However,systematic research on the timing effect of HT on the sequentially developing internode and stem is currently lacking.To identify the timing effect of HT on the morphology and plasticity of the stem in maize,two hybrids(Zhengdan 958(ZD958),Xianyu 335(XY335))characterized by distinct morphological traits in the stem were exposed to a 7-day HT treatment from the V6 to V17 stages(Vn presents the vegetative stage with n leaves fully expanded)in 2019-2020.The results demonstrated that exposure to HT during V6-V12 accelerated the rapid elongation of stems.For instance,HT occurring at V7 and V12 specifically promoted the lengths and weights of the 3rd-5th and 9th-11th internodes,respectively.Meanwhile,HT slowed the growth of internodes adjacent to the promoted internodes.Interestingly,compared with control,the plant height was significantly increased soon after HT treatment,but the promotion effect became narrower at the subsequent flowering stage,demonstrating a self-adjusting mechanism in the maize plant in response to HT.Importantly,HT altered the plant architectures,including a rising of the ear position and increase in the ear position coefficient.XY335 exhibited greater sensitivity in stem development than ZD958 under HT treatment.These findings improve our systematic understanding of the plasticity of internode and plant architecture in response to the timing of HT exposure.
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
文摘Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative therapies.The term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical neurosciences.Indeed,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.
基金supported by on operating grant(#1038154) from the Multiple Sclerosis Society of Canada (to TEK)a Multiple Sclerosis Society of Canada Post-Doctoral Fellowship (to JDMG)。
文摘Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.Myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.
基金Project supported by Guangdong Major Project of Basic and Applied Basic Research,China (Grant No.2019B030302010)the National Natural Science Foundation of China (Grant No.52130108)+1 种基金Guangdong Basic and Applied Basic Research,China (Grant No.2021B1515140005)Pearl River Talent Recruitment Program (Grant No.2021QN02C04)。
文摘Anelasticity, as an intrinsic property of amorphous solids, plays a significant role in understanding their relaxation and deformation mechanism. However, due to the lack of long-range order in amorphous solids, the structural origin of anelasticity and its distinction from plasticity remain elusive. In this work, using frozen matrix method, we study the transition from anelasticity to plasticity in a two-dimensional model glass. Three distinct mechanical behaviors, namely,elasticity, anelasticity, and plasticity, are identified with control parameters in the amorphous solid. Through the study of finite size effects on these mechanical behaviors, it is revealed that anelasticity can be distinguished from plasticity.Anelasticity serves as an intrinsic bridge connecting the elasticity and plasticity of amorphous solids. Additionally, it is observed that anelastic events are localized, while plastic events are subextensive. The transition from anelasticity to plasticity is found to resemble the entanglement of long-range interactions between element excitations. This study sheds light on the fundamental nature of anelasticity as a key property of element excitations in amorphous solids.
基金supported by grants from the NIH,United States (R01AG078728-01 and R21NS113068)Fund-the UTHSC Senator Lloyd and B.A.Bentsen Center for Stroke Research (to JQW)。
文摘Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific functions.Notably,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous system.During development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.
基金supported by Progetto Trapezio,Compagnia di San Paolo(67935-2021.2174)to LB,Fondazione CRT(Cassa di Risparmio di Torino,RF=2022.0618)to LB。
文摘Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Overall,different types of plasticity,including stem cell-driven genesis of new neurons(adult neurogenesis),cells in arrested maturation(dormant neurons),neuro-glial and synaptic plasticity,can coexist and contribute to grant plastic changes in the brain,from a cellular to system level(Benedetti and Couillard-Despres,2022;Bonfanti et al.,2023).
基金the National Key Research and Development Program of China(2022YFC2009700)the National Science Foundation of China(82372582)+1 种基金the Medical Applications Basic Research Project of Suzhou Science and Technology Bureau(SKY2023033)the Wujiang District Science,Education,Health and Promotion Project(WWK202021).
文摘Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticity might represent a potential neurophysiological marker for language function.
文摘The superplastic behavior and associated deformation mechanisms of a fine-grained Mg-10.1 Li-0.8Al-0.6Zn alloy(LAZ1011)with a grain size of 3.2μm,primarily composed of the BCCβphase and a small amount of the HCPαphase,were examined in a temperature range of 473 K to 623 K.The microstructural refinement of this alloy was achieved by employing high-ratio differential speed rolling.The best superplasticity was achieved at 523 K and at strain rates of 10^(-4)-5×10^(-4)s^(-1),where tensile elongations of 550±600%were obtained.During the heating and holding stage of the tensile samples prior to tensile loading,a significant increase in grain size was observed at temperatures above 573 K.Therefore,it was important to consider this effect when analyzing and understanding the superplastic deformation behavior and mechanisms.In the investigated strain rate range,the superplastic flow at low strain rates was governed by lattice diffusion-controlled grain boundary sliding,while at high strain rates,lattice diffusion-controlled dislocation climb creep was the rate-controlling deformation mechanism.It was concluded that solute drag creep is unlikely to occur.During the late stages of deformation at 523 K,it was observed that grain boundary sliding led to the agglomeration of theαphase,resulting in significant strain hardening.Deformation mechanism maps were constructed forβ-Mg-Li alloys in the form of 2D and 3D formats as a function of strain rate,stress,temperature,and grain size,using the constitutive equations for various deformation mechanisms derived based on the data of the current tests.
基金supported by the President Foundation of Nanfang Hospital,Southern Medical University,No.2016Z003(50107021)(to JZF).
文摘Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.
基金supported by the National Natural Science Foundation of China,Nos.81871408 and 81271631(to XMW)National Science Foundation for Young Scientists of China,No.81801658(to YZ)+1 种基金Outstanding Scientific Fund of Shengjing Hospital,No.201402(to XMW)345 Talent Support Project of Shengjing Hospital,No.30B(to YZ)。
文摘Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalities for reducing glutamate accumulation.However,further research is needed to investigate the dynamic changes in and molecular mechanisms of glutamate transport and the effects of glutamate transport on synapses.The aim of this study was to investigate the regulatory mechanisms underlying Notch pathway mediation of glutamate transport and synaptic plasticity.In this study,Yorkshire neonatal pigs(male,age 3 days,weight 1.0–1.5 kg,n=48)were randomly divided into control(sham surgery group)and five hypoxic ischemia subgroups,according to different recovery time,which were then further subdivided into subgroups treated with dimethyl sulfoxide or a Notch pathway inhibitor(N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester).Once the model was established,immunohistochemistry,immunofluorescence staining,and western blot analyses of Notch pathway-related proteins,synaptophysin,and glutamate transporter were performed.Moreover,synapse microstructure was observed by transmission electron microscopy.At the early stage(6–12 hours after hypoxic ischemia)of hypoxic ischemic injury,expression of glutamate transporter excitatory amino acid transporter-2 and synaptophysin was downregulated,the number of synaptic vesicles was reduced,and synaptic swelling was observed;at 12–24 hours after hypoxic ischemia,the Notch pathway was activated,excitatory amino acid transporter-2 and synaptophysin expression was increased,and the number of synaptic vesicles was slightly increased.Excitatory amino acid transporter-2 and synaptophysin expression decreased after treatment with the Notch pathway inhibitor.This suggests that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin.
文摘The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled.To control cognitive function and behavior,the two systems are engaged in a subtle interacting act.In this scenario,a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging.Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes.In this dynamic equilibrium,synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro-and anti-inflammatory molecules in the central nervous system microenvironment.
基金supported by the National Natural Science Foundation of China (U21A20361 and 82130039 to Y.W.Z.)Fundamental Research Funds for the Central Universities (20720220133 to Y.W.Z.)+2 种基金Natural Science Foundation of Fujian Province (2021J02057 to Q.L.M.)Science and Technology Plan Projects of Fujian Province (2020Y2015 to Z.X.W.)2020 Joint Support of Key Projects on Health Care (3502Z20209005 to Z.X.W.)。
文摘Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
基金supported by the Tenure Track Pilot Programme of the Croatian Science FoundationEcole Polytechnique Fédérale de Lausanne and Project TTP-2018-07-9675 Evolution in the Dark,with funds from the Croatian-Swiss Research Programme
文摘Cave animals are an excellent model system for studying adaptive evolution.At present,however,little is known about the mechanisms that enable surface colonizers to survive in the challenging environment of caves.One possibility is that these species have the necessary genetic background to respond with plastic changes to the pressures of underground habitats.To gain insight into this process,we conducted a comparative study with the fish species Telestes karsticus,which occurs in a hydrological system consisting of an interconnected stream and a cave.Results showed that T.karsticus resided year-round and spawned in Sušik cave,making it the first known cavefish in the Dinaric Karst.Cave and surface populations differed in morphological and physiological characteristics,as well as in patterns of gene expression without any evidence of genetic divergence.To test whether observed trait differences were plastic or genetic,we placed adult fish from both populations under light/dark or constant dark conditions.Common laboratory conditions erased all morphometric differences between the two morphs,suggesting phenotypic plasticity is driving the divergence of shape and size in wild fish.Lighter pigmentation and increased fat deposition exhibited by cave individuals were also observed in surface fish kept in the dark in the laboratory.Our study also revealed that specialized cave traits were not solely attributed to developmental plasticity,but also arose from adult responses,including acclimatization.Thus,we conclude that T.karsticus can adapt to cave conditions,with phenotypic plasticity playing an important role in the process of cave colonization.
基金supported by the National Natural Science Foundation of China,Nos.81401002 (to SSZ),81801 053 (to XQZ)。
文摘Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.
文摘The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specialized molecular machinery is strategically placed to release and receive neurotransmitters and to generate and extinguish calcium(Ca^(2+))signals.These synaptic molecular components are highly dynamic and they influence each other to confer structural and functional adaptability(plasticity)to neuronal communication(Biederer et al.,2017).