ASN NEURO最新文献

{"title":"Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration.","authors":"Chen Liang,&nbsp;Damien Carrel,&nbsp;Nisha K Singh,&nbsp;Liam L Hiester,&nbsp;Isabelle Fanget,&nbsp;Hyuck Kim,&nbsp;Bonnie L Firestein","doi":"10.1177/17590914211062765","DOIUrl":"https://doi.org/10.1177/17590914211062765","url":null,"abstract":"<p><p>Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs. Thus, it is important to understand the regulation of PTMs during brain development as multiple developmental processes are dependent on MTs. In this study, we identified that carboxypeptidase E (CPE) changes tubulin polyglutamylation, a major PTM in the brain, and we examine the impact of CPE-mediated changes to polyglutamylation on cortical neuron migration and dendrite morphology. We show, for the first time, that overexpression of CPE increases the level of polyglutamylated α-tubulin while knockdown decreases the level of polyglutamylation. We also demonstrate that CPE-mediated changes to polyglutamylation are dependent on the CPE zinc-binding motif and that this motif is necessary for CPE action on p150^Glued localization. However, overexpression of a CPE mutant that does not increase MT glutamylation mimics the effects of overexpression of wild type CPE on dendrite branching. Furthermore, although overexpression of wild type CPE does not alter cortical neuron migration, overexpression of the mutant may act in a dominant-negative manner as it decreases the number of neurons that reach the cortical plate (CP), as we previously reported for CPE knockdown. Overall, our data suggest that CPE changes MT glutamylation and redistribution of p150^Glued and that this function of CPE is independent of its role in shaping dendrite development but plays a partial role in regulating cortical neuron migration.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211062765"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/3e/10.1177_17590914211062765.PMC8755936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39809789","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}

{"title":"Müller Cell Molecular Heterogeneity: Facts and Predictions","authors":"M. Lamas, Erick J. Martinez-Colin","doi":"10.1177/17590914221106903","DOIUrl":"https://doi.org/10.1177/17590914221106903","url":null,"abstract":"The retina was historically considered as an “approachable part of the brain”; advantageous, for its simplicity, to use as a model organ for deciphering cellular and molecular mechanisms underlying physiology and pathology of the nervous system. However, the most relevant discoveries arise precisely from unveiling the complexity of the retina. A complexity that partially relies on the layered organization of an extended variety of specialized neuronal and glial cellular types and subtypes. Based on functional, morphological or transcriptome data, over 40 subtypes of retinal ganglion cells or 60 subtypes of retinal amacrine cells have been described. A high degree of specialization, that may lead to segregation into functionally diverse subtypes, is also conceivable for Müller cells, a pleiotropic glial component of all vertebrate retinas. The essential role of Müller glia in retinal homeostasis maintenance involves participation in structural, metabolic and intercellular communication processes. Additionally, they are the only retinal cells that possess regenerative potential in response to injury or disease, and thus may be considered as therapeutic tools. In the assumption that functional heterogeneity might be driven by molecular heterogeneity this review aims to compile emerging evidence that could broaden our understanding of Müller cell biology and retinal physiology. Summary statement Müller glial cells exert multiple essential functions in retinal physiology and retinopathies reflecting perhaps the existence of distinct Müller cellular subpopulations. Harnessing Müller cell heterogeneity may serve to enhance new therapeutic approaches for retinal disease.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43324845","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}

{"title":"Astrocyte Cell Surface Antigen 2 and Other Potential Cell Surface Markers of Enteric glia in the Mouse Colon.","authors":"Vladimir Grubišić,&nbsp;Brian D Gulbransen","doi":"10.1177/17590914221083203","DOIUrl":"https://doi.org/10.1177/17590914221083203","url":null,"abstract":"<p><p>Enteric glia regulate gut functions in health and disease through diverse interactions with neurons and immune cells. Intracellular localization of traditional markers of enteric glia such as GFAP, s100b, and Sox10 makes them incompatible for studies that require antigen localization at the cell surface. Thus, new tools are needed for probing the heterogeneous roles of enteric glia at the protein, cell, and functional levels. Here we selected several cell surface antigens including Astrocyte Cell Surface Marker 2 (ACSA2), Cluster of differentiation 9 (CD9), lysophosphatidic acid receptor 1 (LPAR1), and Proteolipid protein 1 (PLP1) as potential markers of enteric glia. We tested their specificity for enteric glia using published single-cell/-nuclei and glia-specific translating mRNA enriched transcriptome datasets, immunolabeling, and flow cytometry. The data show that ACSA2 is a specific marker of mucosal and myenteric glia while other markers are suitable for identifying all subpopulations of enteric glia (LPAR1), glia and immune cells (CD9), or are not suitable for cell-surface labeling (PLP1). These new tools will be useful for future work focused on understanding specific glial functions in health and disease.<b>Summary Statement</b>This study identifies astrocyte cell surface antigen 2 as a novel marker of myenteric glia in the intestine. This, in combination with other markers identified in this study, could be used for selective targeting of enteric glia.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221083203"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/23/10.1177_17590914221083203.PMC9125112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9302672","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}

{"title":"Rab11 and Its Role in Neurodegenerative Diseases.","authors":"Pinky Sultana,&nbsp;Jiri Novotny","doi":"10.1177/17590914221142360","DOIUrl":"https://doi.org/10.1177/17590914221142360","url":null,"abstract":"<p><p>Vesicles mediate the trafficking of membranes/proteins in the endocytic and secretory pathways. These pathways are regulated by small GTPases of the Rab family. Rab proteins belong to the Ras superfamily of GTPases, which are significantly involved in various intracellular trafficking and signaling processes in the nervous system. Rab11 is known to play a key role especially in recycling many proteins, including receptors important for signal transduction and preservation of functional activities of nerve cells. Rab11 activity is controlled by GEFs (guanine exchange factors) and GAPs (GTPase activating proteins), which regulate its function through modulating GTP/GDP exchange and the intrinsic GTPase activity, respectively. Rab11 is involved in the transport of several growth factor molecules important for the development and repair of neurons. Overexpression of Rab11 has been shown to significantly enhance vesicle trafficking. On the other hand, a reduced expression of Rab11 was observed in several neurodegenerative diseases. Current evidence appears to support the notion that Rab11 and its cognate proteins may be potential targets for therapeutic intervention. In this review, we briefly discuss the function of Rab11 and its related interaction partners in intracellular pathways that may be involved in neurodegenerative processes.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221142360"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/55/10.1177_17590914221142360.PMC9726856.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10342452","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}

{"title":"Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper.","authors":"Megan L Morgan,&nbsp;Wulin Teo,&nbsp;Yda Hernandez,&nbsp;Craig Brideau,&nbsp;Karen Cummins,&nbsp;Hedwich F Kuipers,&nbsp;Peter K Stys","doi":"10.1177/17590914221126367","DOIUrl":"https://doi.org/10.1177/17590914221126367","url":null,"abstract":"<p><strong>Summary statement: </strong>The demyelinating effects of CPZ are not due to Cu deficiency but are instead consistent with acute toxicity of a CPZ + Cu complex.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221126367"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/74/10.1177_17590914221126367.PMC9483969.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40365159","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}

{"title":"Disruption of Synaptic Transmission in the Bed Nucleus of the Stria Terminalis Reduces Seizure-Induced Death in DBA/1 Mice and Alters Brainstem E/I Balance","authors":"Maya Y. Xia, Benjamin Owen, J. Chiang, Alyssa Levitt, Katherine Preisinger, W. Yan, Ragan Huffman, W. Nobis","doi":"10.1101/2021.12.23.473665","DOIUrl":"https://doi.org/10.1101/2021.12.23.473665","url":null,"abstract":"Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Accumulating evidence from recent human studies and animal models suggests that seizure-related respiratory arrest may be important for initiating cardiorespiratory arrest and death. Prior evidence suggests that apnea onset can coincide with seizure spread to the amygdala and that stimulation of the amygdala can reliably induce apneas in epilepsy patients, potentially implicating amygdalar regions in seizure-related respiratory arrest and subsequent postictal hypoventilation and cardiorespiratory death. This study aimed to determine if an extended amygdalar structure, the dorsal bed nucleus of the stria terminalis (dBNST), is involved in seizure-induced respiratory arrest (S-IRA) and death using DBA/1 mice, a mouse strain which has audiogenic seizures (AGS) and a high incidence of postictal respiratory arrest and death. The presence of S-IRA significantly increased c-Fos expression in the dBNST of DBA/1 mice. Furthermore, disruption of synaptic output from the dBNST via viral-induced tetanus neurotoxin (TeNT) significantly improved survival following S-IRA in DBA/1 mice without affecting baseline breathing or hypercapnic (HCVR) and hypoxic ventilatory response (HVR). This disruption in the dBNST resulted in changes to the balance of excitatory/inhibitory (E/I) synaptic events in the downstream brainstem regions of the lateral parabrachial nucleus (PBN) and the periaqueductal gray (PAG). These findings suggest that the dBNST is a potential subcortical forebrain site necessary for the mediation of S-IRA, potentially through its outputs to brainstem respiratory regions.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44908187","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}

{"title":"Microglial- and Astrocyte-Specific Expression of Purinergic Signaling Components and Inflammatory Mediators in the Rat Hippocampus During Trimethyltin-Induced Neurodegeneration.","authors":"Milorad Dragić,&nbsp;Nataša Mitrović,&nbsp;Marija Adžić,&nbsp;Nadežda Nedeljković,&nbsp;Ivana Grković","doi":"10.1177/17590914211044882","DOIUrl":"https://doi.org/10.1177/17590914211044882","url":null,"abstract":"<p><p>The present study examined the involvement of purinergic signaling components in the rat model of hippocampal degeneration induced by trimethyltin (TMT) intoxication (8 mg/kg, single intraperitoneal injection), which results in behavioral and neurological dysfunction similar to neurodegenerative disorders. We investigated spatial and temporal patterns of ecto-nucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5' nucleotidase (eN/CD73) activity, their cell-specific localization, and analyzed gene expression pattern and/or cellular localization of purinoreceptors and proinflammatory mediators associated with reactive glial cells. Our study demonstrated that all Iba1+ cells at the injured area, irrespective of their morphology, upregulated NTPDase1/CD39, while induction of eN/CD73 has been observed at amoeboid Iba1+ cells localized within the hippocampal neuronal layers with pronounced cell death. Marked induction of P2Y₁₂R, P2Y₆R, and P2X₄-messenger RNA at the early stage of TMT-induced neurodegeneration might reflect the functional properties, migration, and chemotaxis of microglia, while induction of P2X₇R at amoeboid cells probably modulates their phagocytic role. Reactive astrocytes expressed adenosine A₁, A_2A, and P2Y₁ receptors, revealed induction of complement component C3, inducible nitric oxide synthase, nuclear factor-kB, and proinflammatory cytokines at the late stage of TMT-induced neurodegeneration. An increased set of purinergic system components on activated microglia (NTPDase1/CD39, eN/CD73, and P2X₇) and astrocytes (A₁R, A_2AR, and P2Y₁), and loss of homeostatic glial and neuronal purinergic pathways (P2Y₁₂ and A₁R) may shift purinergic signaling balance toward excitotoxicity and inflammation, thus favoring progression of pathological events. These findings may contribute to a better understanding of the involvement of purinergic signaling components in the progression of neurodegenerative disorders that could be target molecules for the development of novel therapies.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211044882"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/4f/10.1177_17590914211044882.PMC8495514.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476950","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}

{"title":"Innate Immunity and Cell Death in Alzheimer's Disease.","authors":"SangJoon Lee,&nbsp;Hyun-Jeong Cho,&nbsp;Jin-Hyeob Ryu","doi":"10.1177/17590914211051908","DOIUrl":"https://doi.org/10.1177/17590914211051908","url":null,"abstract":"<p><p>The innate immune system plays key roles in controlling Alzheimer's disease (AD), while secreting cytokines to eliminate pathogens and regulating brain homeostasis. Recent research in the field of AD has shown that the innate immune-sensing ability of pattern recognition receptors on brain-resident macrophages, known as microglia, initiates neuroinflammation, Aβ accumulation, neuronal loss, and memory decline in patients with AD. Advancements in understanding the role of innate immunity in AD have laid a strong foundation to elucidate AD pathology and devise therapeutic strategies for AD in the future. In this review, we highlight the present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion in AD. We also discuss how the AD pathology influences these biological processes.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211051908"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/79/10.1177_17590914211051908.PMC8532209.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39535822","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}

{"title":"Intermittent Lipopolysaccharide Exposure Significantly Increases Cortical Infarct Size and Impairs Autophagy.","authors":"Ashley E Russell,&nbsp;John Z Cavendish,&nbsp;Ali Rai,&nbsp;Mya Vannoy,&nbsp;Ahmad H Dakhlallah,&nbsp;Heng Hu,&nbsp;Xuefang Ren,&nbsp;Amal Amer,&nbsp;Candice M Brown,&nbsp;Clay B Marsh,&nbsp;James W Simpkins,&nbsp;Duaa Dakhlallah","doi":"10.1177/1759091421991769","DOIUrl":"https://doi.org/10.1177/1759091421991769","url":null,"abstract":"<p><p>Globally, stroke is a leading cause of death and disability. Traditional risk factors like hypertension, diabetes, and obesity do not fully account for all stroke cases. Recent infection is regarded as changes in systemic immune signaling, which can increase thrombosis formation and other stroke risk factors. We have previously shown that administration of lipopolysaccharide (LPS) 30-minutes prior to stroke increases in infarct volume. In the current study, we found that animals intermittently exposed to LPS have larger cortical infarcts when compared to saline controls. To elucidate the mechanism behind this phenomenon, several avenues were investigated. We observed significant upregulation of tumor necrosis factor-alpha (TNF-α) mRNA, especially in the ipsilateral hemisphere of both saline and LPS exposed groups compared to sham surgery animals. We also observed significant reductions in expression of genes involved in autophagy in the ipsilateral hemisphere of LPS stroke animals. In addition, we assessed DNA methylation of autophagy genes and observed a significant increase in the ipsilateral hemisphere of LPS stroke animals. Intermittent exposure to LPS increases cortical infarct volume, downregulates autophagy genes, and induces hypermethylation of the corresponding CpG islands. These data suggest that intermittent immune activation may deregulate epigenetic mechanisms and promote neuropathological outcomes after stroke.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"1759091421991769"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091421991769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25407418","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}

{"title":"Restoration of Noradrenergic Function in Parkinson's Disease Model Mice.","authors":"Kui Cui,&nbsp;Fan Yang,&nbsp;Turan Tufan,&nbsp;Muhammad U Raza,&nbsp;Yanqiang Zhan,&nbsp;Yan Fan,&nbsp;Fei Zeng,&nbsp;Russell W Brown,&nbsp;Jennifer B Price,&nbsp;Thomas C Jones,&nbsp;Gary W Miller,&nbsp;Meng-Yang Zhu","doi":"10.1177/17590914211009730","DOIUrl":"https://doi.org/10.1177/17590914211009730","url":null,"abstract":"<p><p>Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson's disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211009730"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211009730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38944021","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}