ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211010647
Zheng-Long Jin, Wen-Ying Gao, Shao-Jun Liao, Tao Yu, Qing Shi, Shang-Zhen Yu, Ye-Feng Cai
{"title":"Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis.","authors":"Zheng-Long Jin, Wen-Ying Gao, Shao-Jun Liao, Tao Yu, Qing Shi, Shang-Zhen Yu, Ye-Feng Cai","doi":"10.1177/17590914211010647","DOIUrl":"10.1177/17590914211010647","url":null,"abstract":"<p><p>Intracerebral haemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. It has been reported that paeonol (PAN) inhibits the progression of ICH. However, the mechanism by which paeonol mediates the progression of ICH remains unclear. To mimic ICH <i>in vitro</i>, neuronal cells were treated with hemin. An <i>in vivo</i> model of ICH was established to detect the effect of paeonol on ferroptosis in neurons during ICH. Cell viability was tested by MTT assay. Furthermore, cell injury was detected by GSH, MDA and ROS assays. Ferroptosis was examined by iron assay. RT-qPCR and western blotting were used to detect gene and protein expression, respectively. The correlation among HOTAIR, UPF1 and ACSL4 was explored by FISH, RNA pull-down and RIP assays. Paeonol significantly inhibited the ferroptosis of neurons in ICH mice. In addition, paeonol significantly reversed hemin-induced injury and ferroptosis in neurons, while this phenomenon was notably reversed by HOTAIR overexpression. Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Therefore, paeonol might serve as a new agent for the treatment of ICH.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211010647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38913151","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/1759091421991771
Ruixia Wu, Yue Su, Quan Yuan, Linlin Li, Jimusi Wuri, Xiaoxuan Liu, Tao Yan
{"title":"Sex Effect on Cardiac Damage in Mice With Experimental Autoimmune Encephalomyelitis.","authors":"Ruixia Wu, Yue Su, Quan Yuan, Linlin Li, Jimusi Wuri, Xiaoxuan Liu, Tao Yan","doi":"10.1177/1759091421991771","DOIUrl":"https://doi.org/10.1177/1759091421991771","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Recent clinical study suggested that MS patient exhibited acute heart failure. Further, 12-lead electrocardiographic study showed a longer QTc interval in both MS patient and experimental autoimmune encephalomyelitis (EAE) Lewis rat. However, there is limited study regarding the effect of sex on cardiac injury in EAE. To our knowledge, sex effect on cardiac damage in mice with EAE has not yet been published. Herein, we examined the role of the immune system in mediating cardiac dysfunction after EAE in female and male mice. Neurological function was subsequently evaluated and cardiac function was assessed by echocardiography at multiple time points after EAE. EAE mice exhibited severe neurological deficit and significant cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 2 months after EAE induction. Meanwhile male EAE presented increased expression of the oxidative stress (e.g., nicotinamaide adenine dinucleotide phosphate oxidase-2; NOX-2) in heart, as well as cardiac hypertrophy, increased left ventricle (LV) mass and more severe cardiac fibrosis compared with male control mice. In addition, male EAE mice showed significantly increased cardiac canonical inflammatory mediator (e.g., monocyte chemoattractant protein-1; MCP-1, transforming growth factor-β; TGF-β and toll-like receptor 2; TLR-2) compared with female EAE mice at 2 months after EAE induction. In conclusion, EAE increases inflammatory factor expression and aggravates cardiac dysfunction in male mice compared with female mice, which may contribute to different cardiac outcome in EAE mice.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091421991771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25332551","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211019886
Thatcher B Ladd, James A Johnson, Christen L Mumaw, Hendrik J Greve, Xiaoling Xuei, Ed Simpson, Mark A Barnes, Brett J Green, Tara L Croston, Chandrama Ahmed, Angela Lemons, Donald H Beezhold, Michelle L Block
{"title":"<i>Aspergillus versicolor</i> Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.","authors":"Thatcher B Ladd, James A Johnson, Christen L Mumaw, Hendrik J Greve, Xiaoling Xuei, Ed Simpson, Mark A Barnes, Brett J Green, Tara L Croston, Chandrama Ahmed, Angela Lemons, Donald H Beezhold, Michelle L Block","doi":"10.1177/17590914211019886","DOIUrl":"https://doi.org/10.1177/17590914211019886","url":null,"abstract":"<p><p>Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated <i>Aspergillus versicolo</i>r (3 × 10<sup>5</sup> spores), or viable <i>A. versicolo</i>r (3 × 10<sup>5</sup> spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable <i>A. versicolo</i>r spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory (<i>Tnf and Il1b</i>) and glial activity (<i>Gdnf</i> and <i>Cxc3r1</i>) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of <i>A. versicolo</i>r exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of <i>Drd1</i>, <i>Penk</i>, and <i>Pdyn</i> mRNA expression was confirmed in the 4-week <i>A. versicolo</i>r exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated <i>A. versicolor</i> inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to <i>A. versicolo</i>r inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211019886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39072006","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211019443
Audra York, Angela Everhart, Michael P Vitek, Kirby W Gottschalk, Carol A Colton
{"title":"Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.","authors":"Audra York, Angela Everhart, Michael P Vitek, Kirby W Gottschalk, Carol A Colton","doi":"10.1177/17590914211019443","DOIUrl":"https://doi.org/10.1177/17590914211019443","url":null,"abstract":"<p><p>Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer's disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 (<i>RSAD1</i>) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. <i>APOE4</i> vs <i>APOE3</i> genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211019443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39090013","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":"Sevoflurane-Induced miR-211-5p Promotes Neuronal Apoptosis by Inhibiting Efemp2.","authors":"Yousu Shen, Tao Zhou, Xiaobing Liu, Yanlong Liu, Yaqi Li, Dewu Zeng, Wensheng Zhong, Mingsheng Zhang","doi":"10.1177/17590914211035036","DOIUrl":"https://doi.org/10.1177/17590914211035036","url":null,"abstract":"<p><p>Sevoflurane exposure can result in serious neurological side effects including neuronal apoptosis and cognitive impairment. Although the microRNA miR-211-5p is profoundly upregulated following sevoflurane exposure in neonatal rodent models, the impact of miR-211-5p on neuronal apoptosis and cognitive impairment postsevoflurane exposure has not yet been elucidated. Here, we found that sevoflurane upregulated miR-211-5p and downregulated EGF-Containing Fibulin Extracellular Matrix Protein 2 (Efemp2, Fibulin-4) levels in vitro and in vivo. Sevoflurane's effect on miR-211-5p expression was based on enhancing primary miR-211 transcription. miR-211-5p targets Efemp2's mRNA 3'-untranslated region, reducing Efemp2 expression. RNA immunoprecipitation revealed significant enrichment of the miR-211-5p:Efemp2 mRNA dyad in the RNA-induced silencing complex. miR-211-5p mimics downregulated Efemp2, leading to phosphorylation of Smad2 and Smad3, upregulation of pro-apoptotic Bim, and mitochondrial release of allograft inflammatory factor 1 and cytochrome C. In contrast, miR-211-5p hairpin inhibitor (AntimiR-211-5p) negatively regulated this apoptotic pathway and reduced neuronal apoptosis in an Efemp2-dependent manner. Sevoflurane-exposed mice administered AntimiR-211-5p displayed reduced cortical apoptosis levels and near-term cognitive impairment. In conclusion, sevoflurane-induced miR-211-5p promotes neuronal apoptosis via Efemp2 inhibition. Summary statement: This study revealed the significance of sevoflurane-induced increases in miR-211-5p on the promotion of neuronal apoptosis via inhibition of Efemp2 and its downstream targets.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"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/f2/f9/10.1177_17590914211035036.PMC8819752.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586766","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211038443
Han Xiao, Jianyang Liu, Jialin He, Ziwei Lan, Mingyang Deng, Zhiping Hu
{"title":"17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model.","authors":"Han Xiao, Jianyang Liu, Jialin He, Ziwei Lan, Mingyang Deng, Zhiping Hu","doi":"10.1177/17590914211038443","DOIUrl":"https://doi.org/10.1177/17590914211038443","url":null,"abstract":"<p><p>Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood-brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"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/8a/0b/10.1177_17590914211038443.PMC8580490.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39409464","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211018100
Rongrong Bai, Yue Lang, Jie Shao, Yu Deng, Reyisha Refuhati, Li Cui
{"title":"The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets.","authors":"Rongrong Bai, Yue Lang, Jie Shao, Yu Deng, Reyisha Refuhati, Li Cui","doi":"10.1177/17590914211018100","DOIUrl":"https://doi.org/10.1177/17590914211018100","url":null,"abstract":"<p><p>Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex and a vital component of the immune system. Emerging evidence has indicated that the NLRP3 inflammasome plays an important role in cerebrovascular diseases. The function of the NLRP3 inflammasome in the pathogenesis of cerebrovascular diseases remains an interesting field of research. In this review, we first summarised the pathological mechanism of cerebrovascular diseases and the pathological mechanism of the NLRP3 inflammasome in aggravating atherosclerosis and cerebrovascular diseases. Second, we outlined signalling pathways through which the NLRP3 inflammasome participates in aggravating or mitigating cerebrovascular diseases. Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS/thioredoxin-interacting protein (TXNIP) and purinergic receptor-7 (P2X7R) signalling pathways can activate the NLRP3 inflammasome; activation of the NLRP3 inflammasome can aggravate cerebrovascular diseases by mediating apoptosis and pyroptosis. Autophagy/mitochondrial autophagy, nuclear factor E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) reportedly alleviate cerebrovascular diseases by inhibiting NLRP3 inflammasome activation. Finally, we explored specific inhibitors of the NLRP3 inflammasome based on the two-step activation of the NLRP3 inflammasome, which can be developed as new drugs to treat cerebrovascular diseases.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211018100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032729","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/1759091420982169
Steven M LeVine, Hao Zhu, Sarah E Tague
{"title":"A Simplified Method for the Histochemical Detection of Iron in Paraffin Sections: Intracellular Iron Deposits in Central Nervous System Tissue.","authors":"Steven M LeVine, Hao Zhu, Sarah E Tague","doi":"10.1177/1759091420982169","DOIUrl":"https://doi.org/10.1177/1759091420982169","url":null,"abstract":"<p><p>Although all cells contain iron, most histochemical methods fail to reveal the presence of iron within many cells of the central nervous system (CNS), particularly neurons. Previously, a sensitive method was developed that limited the extraction of iron in paraffin sections, and this method revealed staining within neurons. However, the staining was often too robust making it difficult to discern discrete intracellular structures. In 1970, a study incorporated acetone in an iron histochemical procedure to facilitate the demarcation of staining features. In the present study, both acetone and limits to iron extraction were included in a simplified staining procedure. This procedure was applied to paraffin sections of CNS tissue from CISD2 deficient and littermate control mice. Discrete nuclear and cytoplasmic staining features were detected in all mice. Although widely present in neurons, punctate cytoplasmic staining was particularly prominent in large neurons within the hindbrain. Evaluation of extended depth of focus images, from serial focal planes, revealed numerous stained cytoplasmic structures. Additionally, the simplified staining procedure was applied to paraffin sections from Alzheimer's disease and control cases. Despite suboptimal processing conditions compared to mouse tissue, discrete staining of cytoplasmic structures was revealed in some neurons, although many other neurons had nondescript staining features. In addition, initial findings revealed iron deposited within some vessels from patients with Alzheimer's disease. In summary, since paraffin sections are commonly used for histological preparations, this simplified histochemical procedure could facilitate the study of iron in various CNS conditions by revealing staining details often missed by other procedures.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091420982169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38807589","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}
ASN NEUROPub Date : 2021-01-01DOI: 10.1177/17590914211009851
Robert P Skoff, Denise Bessert, Shreya Banerjee, Xixia Luo, Ryan Thummel
{"title":"Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes.","authors":"Robert P Skoff, Denise Bessert, Shreya Banerjee, Xixia Luo, Ryan Thummel","doi":"10.1177/17590914211009851","DOIUrl":"https://doi.org/10.1177/17590914211009851","url":null,"abstract":"<p><p>A founder mutation in human <i>VPS11</i> (<i>Vacuolar Protein Sorting 11</i>) was recently linked to a genetic leukoencephalopathy in Ashkenazi Jews that presents with the classical features of white matter disorders of the central nervous system (CNS). The neurological deficits include hypomyelination, hypotonia, gradual loss of vision, and seizures. However, the cells expressing the mutation were not identified. Here we describe, using immunocytochemistry, the strong expression of Vps11 in mouse oligodendrocytes and, specifically, its localization with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin. In longitudinal sections of myelin, it forms a bead-like structure, alternating with Myelin Basic Protein (MBP). Immunofluorescent staining with Vps11 and neurofilament proteins indicates the absence of Vps11 in axons <i>in vivo</i>. Finally, changes in Vps11 expression are associated with altered proteolipid protein (PLP) levels based upon mice with duplications or deletions of the <i>Plp1</i> gene. To determine potential functional contributions of Vps11, we combined Vps11 with Platelet Derived Growth Factor Receptor-α (PDGFRα) <i>in vitro</i> and <i>in vivo</i>: in both conditions, co-localization of the two proteins was frequently found in round vesicles of OPCs/oligodendrocytes, suggesting retrograde transport for degradation by the endolysosomal system. Neuron-to-glial communication has been invoked to explain degenerative changes in myelin followed by degenerative changes in axons, and vice versa; but to our knowledge, no specific proteins in retrograde transport from the myelin inner tongue to oligodendrocyte perikarya have been identified. The identification of mutations in <i>VPS11</i> and its localization at the axon-myelin interface should open new avenues of research.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211009851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077084","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}