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Regional brain susceptibility to neurodegeneration: what is the role of Glial cells?

Neural Regeneration Research 2020年第5期15卷 838-842页

作者： Andrea Beatriz Cragnolini Giorgia Lampitella Assunta Virtuoso Immacolata Viscovo Fivos Panetsos Michele Papa Giovanni Cirillo Facultad de Ciencias Exactas Físicas y NaturalesUniversidad Nacional de CórdobaInstituto de Investigaciones Biológicas y Tecnológicas (IIByT)CONICET-Universidad Nacional de CórdobaCórdobaArgentina Human Anatomy and Laboratory of Morphology of Neuronal Networks Department of Mental and Physical Health and Preventive MedicineUniversity of Campania “Luigi VanvitelliNaplesItaly Neuro-computing & Neuro-robotics Research Group Universidad Complutense de MadridNeural Plasticity Research GroupInstituto Investigacion Sanitaria Hospital Clinico San CarlosMadridSpain

The main pathological feature of the neurodegenerative diseases is represented by neuronal death that represents the final step of a cascade of adverse/hostile events.Early in the neurodegenerative process,Glial cells (including astrocytes,microGlial cells,and oligodendrocytes) activate and trigger an insidious neuroinflammatory reaction,metabolic decay,blood brain barrier dysfunction and energy impairment,boosting neuronal death.How these mechanisms might induce selective neuronal death in specific brain areas are far from being elucidated.The last two decades of neurobiological studies have provided evidence of the main role of Glial cells in most of the processes of the central nervous system,from development to synaptogenesis,neuronal homeostasis and integration into,highly specific neuro-Glial networks.In this mini-review,we moved from in vitro and in vivo models of neurodegeneration to analyze the putative role of Glial cells in the early mechanisms of neurodegeneration.We report changes of transcriptional,genetic,morphological,and metabolic activity in astrocytes and microGlial cells in specific brain areas before neuronal degeneration,providing evidence in experimental models of neurodegenerative disorders,including Parkinson’s and Alzheimer’s diseases.Understanding these mechanisms might increase the insight of these processes and pave the way for new specific glia-targeted therapeutic strategies for neurodegenerative disorders.

关键词： astrocytes Glial cells microglia neurodegenerative diseases neuroinflammation Parkinson's disease reactive gliosis selective neuronal degeneration

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Electroacupuncture promotes peripheral nerve regeneration after facial nerve crush injury and upregulates the expression of Glial cell-derived neurotrophic factor

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Neural Regeneration Research 2019年第4期14卷 673-682页

作者： Jing Fei Lin Gao Huan-Huan Li Qiong-Lan Yuan Lei-Ji Li Department of Otorhinolaryngology Head and Neck Surgery Affiliated Hospital of Southwest Medical University Department of Anatomy and Neurobiology Tongji University School of Medicine

The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group(normal control, n = 21), injury group(n = 45) and electroacupuncture group(n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng(TE17), Jiache(ST6), Sibai(ST2), Dicang(ST4), Yangbai(GB14), Quanliao(SI18), and Hegu(LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Wes

关键词： nerve regeneration facial paralysis electroacupuncture Glial cell-derived neurotrophic factor N-cadherin crush injury neuronal apoptosis facial neuron nerve demyelination neural regeneration

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A novel primary culture method for high-purity satellite Glial cells derived from rat dorsal root ganglion

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Neural Regeneration Research 2019年第2期14卷 339-345页

作者： Xian-Bin Wang Wei Ma Tao Luo Jin-Wei Yang Xiang-Peng Wang Yun-Fei Dai Jian-Hui Guo Li-Yan Li Institute of Neuroscience Kunming Medical University Medical Faculty Panzhihua University Second Department of General Surgery First People's Hospital of Yunnan Province

Satellite Glial cells surround neurons within dorsal root ganglia. Previous studies have focused on single-cell suspensions of cultured neurons derived from rat dorsal root ganglia. At present, the primary culture method for satellite Glial cells derived from rat dorsal root ganglia requires no digestion skill. Hence, the aim of the present study was to establish a novel primary culture method for satellite Glial cells derived from dorsal root ganglia. Neonatal rat spine was collected and an incision made to expose the transverse protrusion and remove dorsal root ganglia. Dorsal root ganglia were freed from nerve fibers, connective tissue, and capsule membranes, then rinsed and transferred to 6-well plates, and cultured in a humidified 5% CO_2 incubator at 37°C. After 3 days in culture, some cells had migrated from dorsal root ganglia. After subculture, cells were identified by immunofluorescence labeling for three satellite Glial cell-specific markers: glutamine synthetase, Glial fibrillary acidic protein, and S100β. Cultured cells expressed glutamine synthetase, Glial fibrillary acidic protein, and S100β, suggesting they are satellite Glial cells with a purity of > 95%. Thus, we have successfully established a novel primary culture method for obtaining high-purity satellite Glial cells from rat dorsal root ganglia without digestion.

关键词： nerve regeneration cell culture dorsal root ganglia immunofluorescence identification satellite Glial cells neural regeneration

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Protective role of berberine on ulcerative colitis through modulating enteric Glial cells-intestinal epithelial cells-immune cells interactions

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Acta Pharmaceutica Sinica B 2020年第3期10卷 447-461页

作者： Heng Li Chen Fan Huimin Lu Chunlan Feng Peilan He Xiaoqian Yang Caigui Xiang Jianping Zuo Wei Tang Laboratory of Anti-inflammation and Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesBeijing 100049China Laboratory of Immunology and Virology Shanghai University of Traditional Chinese MedicineShanghai 201203China

Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric Glial cells(EGCs),with decreased Glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.

关键词： Ulcerative colitis Berberine Mucosal inflammation Enteric Glial cells Enteric nervous system

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Differential expression of Glial cell line-derived neurotrophic factor splice variants in the mouse brain

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Neural Regeneration Research 2020年第2期15卷 270-276页

作者： Xiao-He Gu Heng Li Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao Department of Anatomy and Neurobiology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurosurgery First Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.

关键词： Δ78 locus brain region dopaminergic neurons Glial cell line-derived neurotrophic factor mouse brain precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-type repeats splice variants

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Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells

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Neuroscience Bulletin 2019年第1期35卷 167-170页

作者： Xi-Yu Wang Meihua Qu Rui Duan Dengping Shi Ling Jin Jinping Gao Jackie D.Wood Junhua Li Guo-Du Wang Basic and Clinical Medical Research Center Jingmen First Hospital Department of Medicine School of Medicine Tulane University Department of Physiology School of Medicine Ohio State University School of Pharmacy Weifang Medical University Department of Gastroenterology and Surgery Jingmen Second Hospital

Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Their evidence indicates that BPC157 has potent cytoprotection in neural injury and gastrointestinal (GI) ulcers. Nevertheless.

关键词： BPC HT GI Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells

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Insights into the pathogenesis of multiple system atrophy: focus on Glial cytoplasmic inclusions

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Translational Neurodegeneration 2020年第1期9卷 66-80页

作者： Seiji Kaji Takakuni Maki Tomoyuki Ishimoto Hodaka Yamakado Ryosuke Takahashi Department of Neurology Graduate School of MedicineKyoto University54 Shogoin-Kawahara-choSakyo-kuKyotoJapan

Multiple system atrophy(MSA)is a debilitating and fatal neurodegenerative disorder.The disease severity warrants urgent development of disease-modifying therapy,but the disease pathogenesis is still enigmatic.Neurodegeneration in MSA brains is preceded by the emergence of Glial cytoplasmic inclusions(GCIs),which are insoluble α-synuclein accumulations within oligodendrocytes(OLGs).Thus,preventive strategies against GCI formation may suppress disease progression.However,although numerous studies have tried to elucidate the molecular pathogenesis of GCI formation,difficulty remains in understanding the pathological interaction between the two pivotal aspects of GCIs;asynuclein and OLGs.The difficulty originates from several enigmas:1)what triggers the initial generation and possible propagation of pathogenic α-synuclein species?2)what contributes to OLG-specific accumulation of α-synuclein,which is abundantly expressed in neurons but not in OLGs?and 3)how are OLGs and other Glial cells affected and contribute to neurodegeneration?The primary pathogenesis of GCIs may involve myelin dysfunaion and dyshomeostasis of the oligodendroGlial cellular environment such as autophagy and iron metabolism.We have previously reported that oligodendrocyte precursor cells are more prone to develop intracellular inclusions in the presence of extracellular fibrillary α-synuclein.This finding implies a possibility that the propagation of GCI pathology in MSA brains is mediated through the internalization of pathological α-synuclein into oligodendrocyte precursor cells.In this review,in order to discuss the pathogenesis of GCIs,we will focus on the composition of neuronal and oligodendroGlial inclusions in synucleinopathies.Furthermore,we will introduce some hypotheses on how α-synuclein pathology spreads among OLGs in MSA brains,in the light of our data from the experiments with primary oligodendrocyte lineage cell culture.While various reports have focused on the mysterious source of α-synuclein in GCIs,insights into the mechanism wh

关键词： Multiple system atrophy a-synuclein Glial cytoplasmic inclusion Prion Neurodegeneration Oligodendrocyte Microglia Astrocyte Oligodendrocyte precursor cell

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Neural stem cell transplantation inhibits Glial cell proliferation and P2X receptor-mediated neuropathic pain in spinal cord injury rats

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Neural Regeneration Research 2019年第5期14卷 876-885页

作者： Xiao-Jing Du Yue-Xia Chen Zun-Cheng Zheng Nan Wang Xiao-Yu Wang Fan-E Kong Department of Rehabilitation Medicine the Central Hospital of Taian Graduate School Taishan Medical University

P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and Glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of Glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.

关键词： nerve regeneration cell transplantation sensory nerve function Glial fibrillary acidic protein neurofilament P2X4 receptor P2X7 receptor microGlial cells perception threshold hind limb function Glial hyperplasia neural regeneration

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Buyang Huanwu Decoction(补阳还五汤)Attenuates Glial Scar by Downregulating Expression of Leukemia Inhibitory Factor in Intracerebral Hemorrhagic Rats

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Chinese Journal of Integrative Medicine 2019年第4期25卷 264-269页

作者： KANG Xiao ZHOU Hua-jun YANG Jian ZHONG Jian-hua TANG Tao CUI Han-jin ZHOU Jing-hua MEI Zhi-gang Institute of Neurology China Three Gorges UniversityHubei Province(443003)China Department of Neurology The First College of Clinical Medical SciencesChina Three Gorges UniversityHubei Province(443003)China Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine China Three Gorges UniversityYichangHubei Province(443003)China Department of Intensive Care Unit The First College of Clinical Medical SciencesChina Three Gorges UniversityYichangHubei Province(443003)China Institute of Integrative Medicine Xiangya HospitalCentral South UniversityChangsha(410008)China Medical College of China Three Gorges University Hubei Province(443002)China

Objective: To evaluate the effect of Buyang Huanwu Decoction(补阳还五汤,BYHWD) on Glial scar after intracerebral hemorrhage(ICH) and investigate the underlying mechanism.Methods: Collagenase type Ⅶ(0.5 U) was injected stereotaxically into right globus pallidus to induce ICH model.One hundred and twenty SpragueDawley rats were randomly divided into 3 groups according to a random number table,including normal group(n=40),ICH model group(n=40) and BYHWD group(n=40),respectively.After ICH,the rats in the BYHWD group were intragastrically administered with BYHWD(4.36 g/kg) once a day for 21 days,while the rats in ICH group were administered with equal volume of distilled water for 21 days,respectively.Double immunolabeling was performed for proliferating cell nuclear antigen(PCNA)+/Glial ?brillary acidic protein(GFAP)+ nuclei.The expression of GFAP and leukemia inhibitory factor(LIF) was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR).Results: The astrocytes with hypertrophied morphology around the hematoma was observed on day 3 after ICH.The number of GFAP positive cells and GFAP m RNA levels increased notably on day 3 and reached the peak on day 14 post-ICH(PGlial scar by downregulating the expression of LIF in the rats.

关键词： Buyang Huanwu Decoction intracerebral hemorrhage Glial scar leukemia inhibitory factor Chinese medicine

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Transient receptor potential vanilloid 1-immunoreactive signals in murine enteric Glial cells

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World Journal of Gastroenterology 2016年第44期22卷 9752-9764页

作者： Masahiro Yamamoto Mitsue Nishiyama Seiichi Iizuka Shigeaki Suzuki Norihiro Suzuki Sadakazu Aiso Jin Nakahara Tsumura Research Laboratories Tsumura & Co. Department of Neurology Keio University School of Medicine Department of Anatomy Keio University School of Medicine

AIM To investigate the possible involvement of transient receptor potential vanilloid 1(TRPV1) in maturation of enteric Glial cells(EGCs).METHODS Immunohistochemical and immunocytochemical techniques were used to analyze EGC markers in myenteric plexus(MP) as well as cultured MP cells and EGCs using TRPV1 knockout(KO) mice.RESULTS We detected TRPV1-immunoreactive signals in EGC in the MP of wild-type(WT) but not KO mice. Expression of Glial fibrillary acidic protein(GFAP) immunoreactive signals was lower at postnatal day(PD) 6 in KO mice, though the difference was not clear at PD 13 and PD 21. When MP cells were isolated and cultured from isolated longitudinal muscle-MP preparation from WT and KO mice, the yield of KO EGC was lower than that of WT EGC, while the yield of KO and WT smooth muscle cells showed no difference. Addition of BCTC, a TRPV1 antagonist, to enriched EGC culture resulted in a decrease in the protein ratio of GFAP to S100 B, another EGC/astrocyte-specific marker. CONCLUSION These results address the possibility that TRPV1 may be involved in the maturation of EGC, though further studies are necessary to validate this possibility.

关键词： Enteric Glial cells Enteric nervous system Glial fibrillary acidic protein S100B Smooth muscle cells

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