ASN NEURO最新文献_第9页

PACAP Promotes Matrix-Driven Adhesion of Cultured Adult Murine Neural Progenitors. PACAP促进培养的成年小鼠神经祖细胞的基质驱动粘附。

IF 4.7 4区医学

ASN NEURO Pub Date : 2017-05-01 DOI: 10.1177/1759091417708720

James A Waschek, Joseph R Cohen, Gloria C Chi, Tomasz J Proszynski, Pawel Niewiadomski

{"title":"PACAP Promotes Matrix-Driven Adhesion of Cultured Adult Murine Neural Progenitors.","authors":"James A Waschek, Joseph R Cohen, Gloria C Chi, Tomasz J Proszynski, Pawel Niewiadomski","doi":"10.1177/1759091417708720","DOIUrl":"https://doi.org/10.1177/1759091417708720","url":null,"abstract":"New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitor cells (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"9 3","pages":"1759091417708720"},"PeriodicalIF":4.7,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091417708720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35011534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease. 海马体脑源性神经营养因子的条件耗竭加剧了阿尔茨海默病小鼠模型的神经病理学。

IF 4.7 4区医学

ASN NEURO Pub Date : 2017-03-01 DOI: 10.1177/1759091417696161

David J Braun, Sergey Kalinin, Douglas L Feinstein

{"title":"Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease.","authors":"David J Braun, Sergey Kalinin, Douglas L Feinstein","doi":"10.1177/1759091417696161","DOIUrl":"https://doi.org/10.1177/1759091417696161","url":null,"abstract":"Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes to the evolution of neuroinflammation and neurodegeneration in a variety of conditions and diseases. One cause of LC damage may be loss of neurotrophic support from LC target regions. We tested this hypothesis by conditional unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To evaluate the consequences of BDNF loss in the context of neurodegeneration, the mice harbored familial mutations for human amyloid precursor protein and presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion also reduced noradrenergic innervation in the hippocampus, the frontal cortex, and molecular layer of the cerebellum, assessed by staining for dopamine beta hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers and size but was without effect on plaque numbers in the striatum, a site with minimal innervation from the LC. Interestingly, cortical Iba1 staining for microglia was reduced by BDNF depletion and was correlated with reduced dopamine beta hydroxylase staining. These data demonstrate that reduction of BDNF levels in an LC target region can cause retrograde damage to LC neurons, leading to exacerbation of neuropathology in distinct LC target areas. Methods to reduce BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative processes normally limited by LC noradrenergic activities.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"9 2","pages":"1759091417696161"},"PeriodicalIF":4.7,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091417696161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34788487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta C5a增加纤维淀粉样蛋白引起的原代神经元损伤

IF 4.7 4区医学

ASN NEURO Pub Date : 2017-01-01 DOI: 10.1177/1759091416687871

Michael X Hernandez, Pouya Namiranian, E. Nguyen, M. Fonseca, A. Tenner

{"title":"C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta","authors":"Michael X Hernandez, Pouya Namiranian, E. Nguyen, M. Fonseca, A. Tenner","doi":"10.1177/1759091416687871","DOIUrl":"https://doi.org/10.1177/1759091416687871","url":null,"abstract":"C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons. This injury is prevented by the C5aR1 antagonist PMX53, a close analog of PMX205. Furthermore, primary neurons derived from C5aR1 null mice exhibited no MAP-2 loss after exposure to the highest concentration of C5a tested. Primary mouse neurons treated with both 100 nM C5a and 5 µM fibrillar amyloid beta (fAβ), to model what occurs in the AD brain, showed increased MAP-2 loss relative to either C5a or fAβ alone. Blocking C5aR1 with PMX53 (100 nM) blocked the loss of MAP2 in these primary neurons to the level seen with fAβ alone. Similar experiments with primary neurons derived from C5aR1 null mice showed a loss of MAP-2 due to fAβ treatment. However, the addition of C5a to the cultures did not enhance the loss of MAP-2 and the addition of PMX53 to the cultures did not change the MAP-2 loss in response to fAβ. Thus, at least part of the beneficial effects of C5aR1 antagonist in AD mouse models may be due to protection of neurons from the toxic effects of C5a.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416687871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46977346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury. 脊髓损伤后香蜂草与人脐带血干细胞结合的神经保护特性评估

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-11-03 Print Date: 2016-10-01 DOI: 10.1177/1759091416674833

Seyed Ruhollah Hosseini, Gholamreza Kaka, Mohammad Taghi Joghataei, Mehdi Hooshmandi, Seyed Homayoon Sadraie, Kayvan Yaghoobi, Alireza Mohammadi

{"title":"Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury.","authors":"Seyed Ruhollah Hosseini, Gholamreza Kaka, Mohammad Taghi Joghataei, Mehdi Hooshmandi, Seyed Homayoon Sadraie, Kayvan Yaghoobi, Alireza Mohammadi","doi":"10.1177/1759091416674833","DOIUrl":"10.1177/1759091416674833","url":null,"abstract":"Introduction: The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease.Methods: Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination.Results: The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group.Conclusion: The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65580010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways HIV糖蛋白Gp120通过激活Tak1信号通路损害快速轴突运输

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-11-01 DOI: 10.1177/1759091416679073

S. Berth, Nichole A. Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria L. Sapar, G. Morfini, S. Brady

{"title":"HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways","authors":"S. Berth, Nichole A. Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria L. Sapar, G. Morfini, S. Brady","doi":"10.1177/1759091416679073","DOIUrl":"https://doi.org/10.1177/1759091416679073","url":null,"abstract":"Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a mechanistic basis for these effects, pharmacological experiments revealed an involvement of various phosphotransferases in this toxic effect, including members of mitogen-activated protein kinase pathways (Tak-1, p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2), and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and primary cultures extended these findings. Impairments in neurite outgrowth in DRG neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1 mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together, these observations indicate that kinase-based impairments in FAT represent a novel mechanism underlying gp120 neurotoxicity consistent with the dying-back degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific kinase inhibitors might provide a novel therapeutic strategy to prevent axonal degeneration in DSP.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"23 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416679073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65579650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

NCAM1 Polysialylation NCAM1 Polysialylation

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-11-01 DOI: 10.1177/1759091416679074

M. Mehrabian, H. Hildebrandt, G. Schmitt-Ulms

{"title":"NCAM1 Polysialylation","authors":"M. Mehrabian, H. Hildebrandt, G. Schmitt-Ulms","doi":"10.1177/1759091416679074","DOIUrl":"https://doi.org/10.1177/1759091416679074","url":null,"abstract":"Much confusion surrounds the physiological function of the cellular prion protein (PrPC). It is, however, anticipated that knowledge of its function will shed light on its contribution to neurodegenerative diseases and suggest ways to interfere with the cellular toxicity central to them. Consequently, efforts to elucidate its function have been all but exhaustive. Building on earlier work that uncovered the evolutionary descent of the prion founder gene from an ancestral ZIP zinc transporter, we recently investigated a possible role of PrPC in a morphogenetic program referred to as epithelial-to-mesenchymal transition (EMT). By capitalizing on PrPC knockout cell clones in a mammalian cell model of EMT and using a comparative proteomics discovery strategy, neural cell adhesion molecule-1 emerged as a protein whose upregulation during EMT was perturbed in PrPC knockout cells. Follow-up work led us to observe that PrPC regulates the polysialylation of the neural cell adhesion molecule NCAM1 in cells undergoing morphogenetic reprogramming. In addition to governing cellular migration, polysialylation modulates several other cellular plasticity programs PrPC has been phenotypically linked to. These include neurogenesis in the subventricular zone, controlled mossy fiber sprouting and trimming in the hippocampal formation, hematopoietic stem cell renewal, myelin repair and maintenance, integrity of the circadian rhythm, and glutamatergic signaling. This review revisits this body of literature and attempts to present it in light of this novel contextual framework. When approached in this manner, a coherent model of PrPC acting as a regulator of polysialylation during specific cell and tissue morphogenesis events comes into focus.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416679074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65580468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice 移植神经前体融入小鼠纹状体，通过释放促红细胞生成素促进功能恢复

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-10-01 DOI: 10.1177/1759091416676147

S. Carelli, T. Giallongo, C. Viaggi, Zuzana Gombalová, E. Latorre, M. Mazza, F. Vaglini, A. D. Di Giulio, A. Gorio

{"title":"Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice","authors":"S. Carelli, T. Giallongo, C. Viaggi, Zuzana Gombalová, E. Latorre, M. Mazza, F. Vaglini, A. D. Di Giulio, A. Gorio","doi":"10.1177/1759091416676147","DOIUrl":"https://doi.org/10.1177/1759091416676147","url":null,"abstract":"Erythropoietin-releasing neural precursor cells (Er-NPCs) are a subclass of subventricular zone-derived neural progenitors, capable of surviving for 6 hr after death of donor. They present higher neural differentiation. Here, Er-NPCs were studied in animal model of Parkinson’s disease. Dopaminergic degeneration was caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intraperitoneal administration in C57BL/6 mice. The loss of function was evaluated by specific behavioral tests. Er-NPCs (2.5 × 105) expressing the green fluorescent protein were administered by stereotaxic injection unilaterally in the left striatum. At the end of observational research period (2 weeks), most of the transplanted Er-NPCs were located in the striatum, while several had migrated ventrally and caudally from the injection site, up to ipsilateral and contralateral substantia nigra. Most of transplanted cells had differentiated into dopaminergic, cholinergic, or GABAergic neurons. Er-NPCs administration also promoted a rapid functional improvement that was already evident at the third day after cells administration. This was accompanied by enhanced survival of nigral neurons. These effects were likely promoted by Er-NPCs-released erythropoietin (EPO), since the injection of Er-NPCs in association with anti-EPO or anti-EPOR antibodies had completely neutralized the recovery of function. In addition, intrastriatal administration of recombinant EPO mimics the effects of Er-NPCs. We suggest that Er-NPCs, and cells with similar properties, may represent good candidates for cellular therapy in neurodegenerative disorders of this kind.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416676147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65579864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy. 在新生儿缺氧缺血性脑病大鼠模型中，鼻内给药干扰素β通过JAK1/STAT3/BCL-2途径减弱神经元凋亡

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-09-28 Print Date: 2016-10-01 DOI: 10.1177/1759091416670492

Brandon J Dixon, Di Chen, Yang Zhang, Jerry Flores, Jay Malaguit, Derek Nowrangi, John H Zhang, Jiping Tang

{"title":"Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Brandon J Dixon, Di Chen, Yang Zhang, Jerry Flores, Jay Malaguit, Derek Nowrangi, John H Zhang, Jiping Tang","doi":"10.1177/1759091416670492","DOIUrl":"10.1177/1759091416670492","url":null,"abstract":"Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2). Intranasal administration of human recombinant IFNβ occurred 2 hr after HIE and infarct volume, body weight, neurobehavioral tests, histology, immunohistochemistry, brain water content, blood-brain barrier permeability, enzyme-linked immunosorbent assay, and Western blot were all used to evaluate various parameters. The results showed that both IFNβ and the Type 1 interferon receptor expression decreases after HIE. Intranasal administration of human recombinant IFNβ was able to be detected in the central nervous system and was able to reduce brain infarction volumes and improve neurological behavior tests 24 hr after HIE. Western blot analysis also revealed that human recombinant IFNβ treatment stimulated Stat3 and Bcl-2 expression leading to a decrease in cleaved caspase-3 expression after HIE. Positive Fluoro-Jade C staining also demonstrated that IFNβ treatment was able to decrease neuronal apoptosis. Furthermore, the beneficial effects of IFNβ treatment were reversed when a Stat3 inhibitor was applied. Also an intraperitoneal administration of human recombinant IFNβ into the systemic compartment was unable to confer the same protective effects as intranasal IFNβ treatment.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416670492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65579370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Knockdown of Unconventional Myosin ID Expression Induced Morphological Change in Oligodendrocytes. 敲除非常规肌球蛋白ID的表达可诱导少突胶质细胞的形态变化

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-09-21 Print Date: 2016-10-01 DOI: 10.1177/1759091416669609

Reiji Yamazaki, Tomoko Ishibashi, Hiroko Baba, Yoshihide Yamaguchi

{"title":"Knockdown of Unconventional Myosin ID Expression Induced Morphological Change in Oligodendrocytes.","authors":"Reiji Yamazaki, Tomoko Ishibashi, Hiroko Baba, Yoshihide Yamaguchi","doi":"10.1177/1759091416669609","DOIUrl":"10.1177/1759091416669609","url":null,"abstract":"Myelin is a special multilamellar structure involved in various functions in the nervous system. In the central nervous system, the oligodendrocyte (OL) produces myelin and has a unique morphology. OLs have a dynamic membrane sorting system associated with cytoskeletal organization, which aids in the production of myelin. Recently, it was reported that the assembly and disassembly of actin filaments is crucial for myelination. However, the partner myosin molecule which associates with actin filaments during the myelination process has not yet been identified. One candidate myosin is unconventional myosin ID (Myo1d) which is distributed throughout central nervous system myelin; however, its function is still unclear. We report here that Myo1d is expressed during later stages of OL differentiation, together with myelin proteolipid protein (PLP). In addition, Myo1d is distributed at the leading edge of the myelin-like membrane in cultured OL, colocalizing mainly with actin filaments, 2',3'-cyclic nucleotide phosphodiesterase and partially with PLP. Myo1d-knockdown with specific siRNA induces significant morphological changes such as the retraction of processes and degeneration of myelin-like membrane, and finally apoptosis. Furthermore, loss of Myo1d by siRNA results in the impairment of intracellular PLP transport. Together, these results suggest that Myo1d may contribute to membrane dynamics either in wrapping or transporting of myelin membrane proteins during formation and maintenance of myelin.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65579414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice Zfp191null和Shiverer (Mbpshi)小鼠髓鞘退化的转录指纹图谱

IF 4.7 4区医学

ASN NEURO Pub Date : 2016-09-01 DOI: 10.1177/1759091416670749

J. Aaker, B. Elbaz, Yuwen Wu, T. Looney, Li Zhang, B. Lahn, B. Popko

{"title":"Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice","authors":"J. Aaker, B. Elbaz, Yuwen Wu, T. Looney, Li Zhang, B. Lahn, B. Popko","doi":"10.1177/1759091416670749","DOIUrl":"https://doi.org/10.1177/1759091416670749","url":null,"abstract":"The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191 null ), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro. To determine whether the loss of myelin seen in Zfp191 null mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient. Interestingly, Mbp shi (shiverer) mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091416670749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65579490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11