Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fa...Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.展开更多
The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the...The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the CNS,orchestrate a wide range of essential activities(Allen and Lyons,2018).Notably,glial cells,which outnumber neurons,constitute the major population within the CNS.This population comprises astrocytes,microglia,oligodendrocytes,and ependymal cells,each fulfilling specialized functions that contribute to neural homeostasis and overall CNS integrity.Astrocytes are pivotal in preserving structural and functional integrity through the regulation of synaptic function,the clearance of neurotransmitters,and ion balance.Moreover,they provide metabolic support to neurons.展开更多
Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investiga...Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.展开更多
Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume respon...Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an...The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an integral role in maintaining homeostasis,neurovascular coupling,and synaptic transmission.Radial astroglia are recognized as a potential source for the generation of new neurons in the brain,a process known as neurogenesis,accounting for neuroplasticity.While brain-resident astrocytes have been extensively studied,increasing experimental evidence has demonstrated the presence of astroglial-like cells in various organs,including the heart.The existence of astrocyte-like cells in the heart,known as cardiac nexus glia,is recognized as an emerging key modulator of cardiac function and blood flow.Similar to astrocytes,cardiac nexus glia can also release different gliotransmitters,including brain-derived neurotrophic factor,thereby modulating neurocardiac interactions.This review delves into the mechanistic insights of the cardiac nexus glia and emphasizes a hypothesis that these glial cells may possess the multipotent capacity to generate neurons,astrocytes,and oligodendrocytes,suggesting that peripheral neurogenesis could occur in the heart.As astrocytes are vital for neuroplasticity,the regulation of cardiac nexus glia may support heart–brain communication,while their dysfunction could lead to neurocardiac disorders.展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
AIM:To investigate the effects and the underlying mechanism(s)of conbercept on the phagocytosis of hard exudates(HEs)by Müller glia in diabetic retinopathy(DR).METHODS:Twenty-one eyes from 17 patients with diabet...AIM:To investigate the effects and the underlying mechanism(s)of conbercept on the phagocytosis of hard exudates(HEs)by Müller glia in diabetic retinopathy(DR).METHODS:Twenty-one eyes from 17 patients with diabetic macular edema(DME)underwent optical coherence tomography(OCT)imaging to examine the changes of HEs before and after intravitreal conbercept injection(IVC).In vitro,rat retinal Müller cell line(rMC-1)was cultured under high glucose and treated with oxidized low-density lipoprotein(Ox-LDL)with or without conbercept.Phagocytosis was analysed with immunofluorescence,flow cytometry,and Western blot.Expressions of scavenger receptors(LOX-1,CD36)were analyzed by quantitative real-time polymerase chain reaction(qRT-PCR).Conbercept’s effects on vascular endothelial growth factor A(VEGF-A),VEGFR2,inflammation(NF-κB,IL-6,iNOS),and oxidative stress(ROS)were evaluated with Western blot and immunofluorescence.RESULTS:The area of HEs showed minimal change after the first IVC(1.39±1.41 to 1.38±1.3 mm2,P=0.938),but significantly decreased after the third IVC(0.45±0.66 mm2,P=0.002).In vitro,conbercept enhanced the phagocytosis of Ox-LDL by rMC-1 cells under high glucose condition.Conbercept reduced ROS and inflammation(NF-κB,IL-6,iNOS)in high glucose-treated rMC-1 cells by suppression of VEGF/VEGFR2 pathway.The inhibition of NF-κB by conbercept further activated PPARγ-CD36 axis,increasing CD36 expression and promoting Ox-LDL uptake,thereby facilitating the clearance of HEs.CONCLUSION:Conbercept reduces HEs in DR by enhancing Müller glia phagocytosis possibly through activating PPARγ-CD36 axis,which is mediated by inhibition of VEGF signaling.Modulation of Müller glia phagocytic capacity might provide a novel therapeutic strategy to treat DR and DME.展开更多
Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Unde...Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].展开更多
This paper is a systematic review of the treatment of bipolar disorder: a systematic Google Scholar search aimed at treatment guidelines and clinical trials. The search for treatment guidelines returned 375 papers and...This paper is a systematic review of the treatment of bipolar disorder: a systematic Google Scholar search aimed at treatment guidelines and clinical trials. The search for treatment guidelines returned 375 papers and was last performed from June 1, 2022 to August 30, 2022. The literature suggests that lithium helps control and alleviate severe mood episodes, and olanzapine is effective for acute manic or mixed episodes of bipolar I disorder. Achieving effectiveness or remission is better with Cariprazine. Lurasidone improves cognitive performance. Quetiapine improves sleep quality and co-morbid anxiety. Lamotrigine helps delay depression, mania, and mild manic episodes. Antidepressants are best used in conjunction with mood stabilizers. For co-morbid treatment, carbamazepine and lithium in combination are more effective in the treatment of psychotic mania. Co-morbid anxiety treatment considers adjunctive olanzapine or lamotrigine. Co-morbid bulimia treatment considers a mood stabilizer. Co-morbid fatigue treatment considers a dawn simulator. For diet, pay attention to a healthy diet, patients can ingest probiotics and pay attention to the balance of fatty acids.展开更多
Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI...Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.展开更多
MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which ...MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.展开更多
The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex i...The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently, some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neuro- gliopathies.展开更多
Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein...Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.展开更多
Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and surv...Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.展开更多
Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia...Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.展开更多
Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to t...Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.展开更多
Background:Microglia are brain resident macrophages originating from mesodermal/mesenchymal cells that migrate into the CNS as early as embryonic day 9 in mice(E9)prior to the emergence of neurons and other glia.They ...Background:Microglia are brain resident macrophages originating from mesodermal/mesenchymal cells that migrate into the CNS as early as embryonic day 9 in mice(E9)prior to the emergence of neurons and other glia.They have variety of neuro-developmental and homeostatic functions during early embryonic central nervous system development and later in the adult brain.They may be responsible for mediating some gender-related structural and functional differences in the brain.Accordingly,identifying the microglia content and amount of migrated microglia in embryonic stage would be helpful to determine the function of microglia in induction of brain gender-related differences.Because of its complexity to determine the exact number of microglia in embryo,and since most studies harvest microglia form neonate mice,but it is not completely determined yet if there is any difference in the content of microglia in male and female neonates.Methods:Brains were extracted from male and female neonates to prepare mixed glia,then microglia were extracted from cultured mixed glia using shaking incubator.Isolated microglia were counted,cultured and gone under microscopic and flow cytometry assays.Results:The number of microglia harvested from male and female pubs is different and presumably male pubs have more microglia ab initio.Morphological assessments on presence of amoeboid,rod like and ramified types showed that both genders have similar ratios.Conclusion:Presence of a greater number of ab initio microglia in male neonates could indicate that gender-difference in the number of microglia may play a role in gender-dependent brain development from infancy.展开更多
The intestinal epithelium constitutes a physical and functional barrier between the external environment and the host organism. It is formed by a continuous monolayer of intestinal epithelial cells maintained together...The intestinal epithelium constitutes a physical and functional barrier between the external environment and the host organism. It is formed by a continuous monolayer of intestinal epithelial cells maintained together by intercellular junctional complex, limiting access of pathogens, toxins and xenobiotics to host tissues. Once this barrier integrity is disrupted, inflammatory disorders and tissue injury are initiated and perpetuated. Beneath the intestinal epithelial cells lies a population of astrocyte-like cells that are known as enteric glia. The morphological characteristics and expression markers of these enteric glia cells were identical to the astrocytes of the central nervous system. In the past few years, enteric glia have been demonstrated to have a trophic and supporting relationship with intestinal epithelial cells. Enteric glia lesions and/or functional defects can be involved in the barrier dysfunction. Besides, factors secreted by enteric glia are important for the regulation of gut barrier function. Moreover, enteric glia have an important impact on epithelial cell transcriptome and induce a shift in epithelial cell phenotype towards increased cell adhesion and cell differentiation.Enteric glia can also preserve epithelial barrier against intestinal bacteria insult. In this review, we will describe the current body of evidence supporting functional roles of enteric glia on intestinal barrier.展开更多
The neuro-glial interface extends far beyond mechanical support alone and includes interactions through coagulation cascade proteins. Here, we systematically review the evidence indicating that synaptic and node of Ra...The neuro-glial interface extends far beyond mechanical support alone and includes interactions through coagulation cascade proteins. Here, we systematically review the evidence indicating that synaptic and node of Ranvier glia cell components modulate synaptic transmission and axonal conduction by a coagulation cascade protein system, leading us to propose the concept of the neuro-glial coagulonome. In the peripheral nervous system, the main thrombin receptor protease activated receptor 1 (PAR1) is located on the Schwann microvilli at the node of Ranvier and at the neuromuscular junction. PAR1 activation effects can be both neuroprotective or harmful, depending on thrombin activity levels. Low physiological levels of thrombin induce neuroprotective effects in the Schwann cells which are mediated by the endothelial protein C receptor. High levels of thrombin induce conduction deficits, as found in experimental autoimmune neuritis, the animal model for Guillaine-Barre syndrome. In the central nervous system, PAR1 is located on the peri-synaptic astrocyte end-feet. Its activation by high thrombin levels is involved in the pathology of primary inflammatory brain diseases such as multiple sclerosis, as well as in other central nervous system insults, including trauma, neoplasms, epilepsy and vascular injury. Following activation of PAR1 by high thrombin levels the seizure threshold is lowered. On the other hand, PAR1 activation by lower levels of thrombin in the central nervous system protects against a future ischemic insult. This review presents the known structure and function of the neuro-glial coagulonome, focusing on coagulation, thrombin and PAR1 in a pathway which may be either physiological (neuroprotective) or detrimental in peripheral nervous system and central nervous system diseases. Understanding the neuro-glial coagulonome may open opportunities for novel pharmacological interventions in neurological diseases.展开更多
基金funded by a grant of the Deutsche Forschungsgemeinschaft(DFG)(SFB 1348,B5)to CK.
文摘Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.
基金supported by Linea D.1.2023-24 UniversitàCattolica del S.Cuore(to MTV).
文摘The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the CNS,orchestrate a wide range of essential activities(Allen and Lyons,2018).Notably,glial cells,which outnumber neurons,constitute the major population within the CNS.This population comprises astrocytes,microglia,oligodendrocytes,and ependymal cells,each fulfilling specialized functions that contribute to neural homeostasis and overall CNS integrity.Astrocytes are pivotal in preserving structural and functional integrity through the regulation of synaptic function,the clearance of neurotransmitters,and ion balance.Moreover,they provide metabolic support to neurons.
基金supported by the National Natural Science Foundation of China,Nos.81970820(to HX),31771644(to JL),31930068(to JL),82371176(to JL),81801331(to LC)National Key Research and Development Project of China.Nos.2017YFA0104100(to JL),2017YFA0701304(to HX)+1 种基金Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)Talent Introduction Plan,No.KYPT202204(to LC)the Fundamental Research Funds for the Central Universities,No.22120230292(to JL)。
文摘Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.
基金supported by the National Natural Science Foundation of China,No.31930068National Key Research and Development Program of China,Nos.2018YFA0107302 and 2021YFA1101203(all to HX).
文摘Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金Supported by UGC-FRPRashtriya Uchchatar Shiksha Abhiyan(RUSA)2.0,Biological Sciences,Bharathidasan University,No.TN RUSA:311/RUSA(2.0)/2018+1 种基金Anusandhan National Research Foundation(ANRF)/Science Engineering Research Board(SERB),No.CRG/2023/005266and UGC-SAP and DST-FIST to the Department of Animal Science,Bharathidasan University.
文摘The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an integral role in maintaining homeostasis,neurovascular coupling,and synaptic transmission.Radial astroglia are recognized as a potential source for the generation of new neurons in the brain,a process known as neurogenesis,accounting for neuroplasticity.While brain-resident astrocytes have been extensively studied,increasing experimental evidence has demonstrated the presence of astroglial-like cells in various organs,including the heart.The existence of astrocyte-like cells in the heart,known as cardiac nexus glia,is recognized as an emerging key modulator of cardiac function and blood flow.Similar to astrocytes,cardiac nexus glia can also release different gliotransmitters,including brain-derived neurotrophic factor,thereby modulating neurocardiac interactions.This review delves into the mechanistic insights of the cardiac nexus glia and emphasizes a hypothesis that these glial cells may possess the multipotent capacity to generate neurons,astrocytes,and oligodendrocytes,suggesting that peripheral neurogenesis could occur in the heart.As astrocytes are vital for neuroplasticity,the regulation of cardiac nexus glia may support heart–brain communication,while their dysfunction could lead to neurocardiac disorders.
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金Supported by the National Natural Science Foundation of China(No.82171062,No.82301222,No.32201244).
文摘AIM:To investigate the effects and the underlying mechanism(s)of conbercept on the phagocytosis of hard exudates(HEs)by Müller glia in diabetic retinopathy(DR).METHODS:Twenty-one eyes from 17 patients with diabetic macular edema(DME)underwent optical coherence tomography(OCT)imaging to examine the changes of HEs before and after intravitreal conbercept injection(IVC).In vitro,rat retinal Müller cell line(rMC-1)was cultured under high glucose and treated with oxidized low-density lipoprotein(Ox-LDL)with or without conbercept.Phagocytosis was analysed with immunofluorescence,flow cytometry,and Western blot.Expressions of scavenger receptors(LOX-1,CD36)were analyzed by quantitative real-time polymerase chain reaction(qRT-PCR).Conbercept’s effects on vascular endothelial growth factor A(VEGF-A),VEGFR2,inflammation(NF-κB,IL-6,iNOS),and oxidative stress(ROS)were evaluated with Western blot and immunofluorescence.RESULTS:The area of HEs showed minimal change after the first IVC(1.39±1.41 to 1.38±1.3 mm2,P=0.938),but significantly decreased after the third IVC(0.45±0.66 mm2,P=0.002).In vitro,conbercept enhanced the phagocytosis of Ox-LDL by rMC-1 cells under high glucose condition.Conbercept reduced ROS and inflammation(NF-κB,IL-6,iNOS)in high glucose-treated rMC-1 cells by suppression of VEGF/VEGFR2 pathway.The inhibition of NF-κB by conbercept further activated PPARγ-CD36 axis,increasing CD36 expression and promoting Ox-LDL uptake,thereby facilitating the clearance of HEs.CONCLUSION:Conbercept reduces HEs in DR by enhancing Müller glia phagocytosis possibly through activating PPARγ-CD36 axis,which is mediated by inhibition of VEGF signaling.Modulation of Müller glia phagocytic capacity might provide a novel therapeutic strategy to treat DR and DME.
基金supported by the National Natural Science Foundation of China(32300959)a Guangzhou Scientific Research Grant(SL2024A04J00578)the SCNU Young Faculty Development Program(22KJ04).
文摘Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].
文摘This paper is a systematic review of the treatment of bipolar disorder: a systematic Google Scholar search aimed at treatment guidelines and clinical trials. The search for treatment guidelines returned 375 papers and was last performed from June 1, 2022 to August 30, 2022. The literature suggests that lithium helps control and alleviate severe mood episodes, and olanzapine is effective for acute manic or mixed episodes of bipolar I disorder. Achieving effectiveness or remission is better with Cariprazine. Lurasidone improves cognitive performance. Quetiapine improves sleep quality and co-morbid anxiety. Lamotrigine helps delay depression, mania, and mild manic episodes. Antidepressants are best used in conjunction with mood stabilizers. For co-morbid treatment, carbamazepine and lithium in combination are more effective in the treatment of psychotic mania. Co-morbid anxiety treatment considers adjunctive olanzapine or lamotrigine. Co-morbid bulimia treatment considers a mood stabilizer. Co-morbid fatigue treatment considers a dawn simulator. For diet, pay attention to a healthy diet, patients can ingest probiotics and pay attention to the balance of fatty acids.
文摘Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.
基金supported by the Singapore National Research Foundation under its NMRC-CBRG grants(Project award number:NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Councilpartially supported by the MOE Academic Research Funding(AcRF) Tier 1 grant(RG148/14) and Tier 2 grant(MOE2015-T2-1-023)
文摘MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.
文摘The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently, some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neuro- gliopathies.
基金supported by the Natural Science Foundation of Guangdong Province,No.2020A1515010090(to ZLZ)the Science and Technology Project Foundation of Guangzhou City,No.202002030004(to HZ).
文摘Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.
基金supported by NIH R01NS103981 and R01CA273586(to CW)。
文摘Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.
基金supported by Canadian Spinal Research Organization, No. #84831
文摘Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.
基金the scope of the CICS-UBI projects UIDP/Multi/00709/2019,UIDB/Multi/00709/2019,UIDP/00709/2020,UIDB/00709/2020,financed by national funds through the Portuguese Foundation for Science and Technology/MCTESby funds to the PPBI-Portuguese Platform of Bio Imaging through the Project POCI-01-0145-FEDER-022122(to GB,MVP,NP)supported by a grant from the Portuguese Foundation for Science and Technology/MCTES(2021.07854.BD)(to IS)。
文摘Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.
文摘Background:Microglia are brain resident macrophages originating from mesodermal/mesenchymal cells that migrate into the CNS as early as embryonic day 9 in mice(E9)prior to the emergence of neurons and other glia.They have variety of neuro-developmental and homeostatic functions during early embryonic central nervous system development and later in the adult brain.They may be responsible for mediating some gender-related structural and functional differences in the brain.Accordingly,identifying the microglia content and amount of migrated microglia in embryonic stage would be helpful to determine the function of microglia in induction of brain gender-related differences.Because of its complexity to determine the exact number of microglia in embryo,and since most studies harvest microglia form neonate mice,but it is not completely determined yet if there is any difference in the content of microglia in male and female neonates.Methods:Brains were extracted from male and female neonates to prepare mixed glia,then microglia were extracted from cultured mixed glia using shaking incubator.Isolated microglia were counted,cultured and gone under microscopic and flow cytometry assays.Results:The number of microglia harvested from male and female pubs is different and presumably male pubs have more microglia ab initio.Morphological assessments on presence of amoeboid,rod like and ramified types showed that both genders have similar ratios.Conclusion:Presence of a greater number of ab initio microglia in male neonates could indicate that gender-difference in the number of microglia may play a role in gender-dependent brain development from infancy.
基金Supported by the National Natural Science Foundation of China,NSFC,No.81200270the Scientific Research Foundation for Outstanding Young Scientist of Shandong Province,No.BS2012SW012
文摘The intestinal epithelium constitutes a physical and functional barrier between the external environment and the host organism. It is formed by a continuous monolayer of intestinal epithelial cells maintained together by intercellular junctional complex, limiting access of pathogens, toxins and xenobiotics to host tissues. Once this barrier integrity is disrupted, inflammatory disorders and tissue injury are initiated and perpetuated. Beneath the intestinal epithelial cells lies a population of astrocyte-like cells that are known as enteric glia. The morphological characteristics and expression markers of these enteric glia cells were identical to the astrocytes of the central nervous system. In the past few years, enteric glia have been demonstrated to have a trophic and supporting relationship with intestinal epithelial cells. Enteric glia lesions and/or functional defects can be involved in the barrier dysfunction. Besides, factors secreted by enteric glia are important for the regulation of gut barrier function. Moreover, enteric glia have an important impact on epithelial cell transcriptome and induce a shift in epithelial cell phenotype towards increased cell adhesion and cell differentiation.Enteric glia can also preserve epithelial barrier against intestinal bacteria insult. In this review, we will describe the current body of evidence supporting functional roles of enteric glia on intestinal barrier.
文摘The neuro-glial interface extends far beyond mechanical support alone and includes interactions through coagulation cascade proteins. Here, we systematically review the evidence indicating that synaptic and node of Ranvier glia cell components modulate synaptic transmission and axonal conduction by a coagulation cascade protein system, leading us to propose the concept of the neuro-glial coagulonome. In the peripheral nervous system, the main thrombin receptor protease activated receptor 1 (PAR1) is located on the Schwann microvilli at the node of Ranvier and at the neuromuscular junction. PAR1 activation effects can be both neuroprotective or harmful, depending on thrombin activity levels. Low physiological levels of thrombin induce neuroprotective effects in the Schwann cells which are mediated by the endothelial protein C receptor. High levels of thrombin induce conduction deficits, as found in experimental autoimmune neuritis, the animal model for Guillaine-Barre syndrome. In the central nervous system, PAR1 is located on the peri-synaptic astrocyte end-feet. Its activation by high thrombin levels is involved in the pathology of primary inflammatory brain diseases such as multiple sclerosis, as well as in other central nervous system insults, including trauma, neoplasms, epilepsy and vascular injury. Following activation of PAR1 by high thrombin levels the seizure threshold is lowered. On the other hand, PAR1 activation by lower levels of thrombin in the central nervous system protects against a future ischemic insult. This review presents the known structure and function of the neuro-glial coagulonome, focusing on coagulation, thrombin and PAR1 in a pathway which may be either physiological (neuroprotective) or detrimental in peripheral nervous system and central nervous system diseases. Understanding the neuro-glial coagulonome may open opportunities for novel pharmacological interventions in neurological diseases.
