ASN NEURO最新文献

{"title":"In Memoriam, Dr. Robert K. Yu.","authors":"Thomas N Seyfried, Yutaka Itokazu, Toshio Ariga, Erhard Bieberich","doi":"10.1177/17590914221146888","DOIUrl":"https://doi.org/10.1177/17590914221146888","url":null,"abstract":"Dr. Robert K. Yu, affectionately known to most of his friends and colleagues as “Bob,” passed away peacefully on May 18, 2022, at the age of 84. Bob served as President of the American Society of Neurochemistry (ASN) from 2001 to 2003 where he instituted a number of foundational changes that improved membership and strengthened financial solvency (Figure 1). Bob received his BS in Chemistry from Tunghai University, Taiwan, in 1960. He received his PhD in Biochemistry from the University of Illinois Urbana/ Champaign in 1967 under the mentorship of Dr. Herbert E. Carter, a member of the National Academy of Sciences. Bob followed in the footsteps of his beloved and accomplished mother, Dr. June Yu, who graduated from the University of Illinois Urbana/Champaign with a PhD in Chemistry and was a pioneer as the first Chinese woman to receive a PhD in Chemistry in the US. Bob completed postdoctoral training in the Department of Neurology at the Albert Einstein College of Medicine/Yeshiva University from 1967 to 1972 under the mentorship of Dr. Robert W. Ledeen, a long-standing member of ASN. Bob began his long and distinguished scientific career as an Assistant Professor in the Departments of Neurology and Molecular Biology and Biochemistry at Yale University in 1973. Bob was rapidly promoted to tenured Professor where he worked until 1988. Bob received a Med. Sci. D. honorary degree from the University of Tokyo in 1980 and an M.A.H. honorary degree from Yale University in 1985. Bob was recruited as Chair and Professor of the Department of Biochemistry and Molecular Biophysics at the Medical College of Virginia/Virginia Commonwealth University. In 2000, Bob was recruited as Director and Professor of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia and served in that capacity until 2009. He also served as President of the Society of Chinese Bioscientists in America from 2008 to 2010. He held the Chair of Georgia Research Alliance Eminent Scholar in Molecular and Cellular Neurobiology, and was the Founding Director of the Institute of Neuroscience at Georgia Health Sciences University, now Augusta University, until his death. Bob’s major research interests were in neurochemistry and developmental neurobiology, particularly as related to glcoconjugates in health and diseases. He published over 400 peer-reviewed scientific papers and served as a senior editor in several high-profile scientific journals including Journal of Lipid Research, Journal of Biological Chemistry, and ASN Neuro. Bob was widely regarded as a leader in the field of glycosphingolipid research. He widely supported the expansion of the Japan Oil Chemists’ Society. For over 40 years, he and his research teams characterized numerous glycosphingolipid structures and elucidated their biophysical properties, biosynthetic pathways, and biological functions. Bob and Dr. Robert Ledeen were the first to demonstrate that the naturally occurring sialidase-susceptib","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914221146888"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/68/10.1177_17590914221146888.PMC9841836.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9190293","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":"Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Astrocytes from Humanized Targeted Replacement Mice.","authors":"Isha Mhatre-Winters,&nbsp;Aseel Eid,&nbsp;Yoonhee Han,&nbsp;Kim Tieu,&nbsp;Jason R Richardson","doi":"10.1177/17590914221144549","DOIUrl":"https://doi.org/10.1177/17590914221144549","url":null,"abstract":"<p><p>Apolipoprotein E4 (APOE4) genotype and sex are significant risk factors for Alzheimer's disease (AD), with females demonstrating increased risk modulated by APOE genotype. APOE is predominantly expressed in astrocytes, however, there is a lack of comprehensive assessments of sex differences in astrocytes stratified by APOE genotype. Here, we examined the response of mixed-sex and sex-specific neonatal APOE3 and APOE4 primary mouse astrocytes (PMA) to a cytokine mix of IL1b, TNFa, and IFNg. Pro-inflammatory and anti-inflammatory cytokine profiles were assessed by qRT-PCR and Meso Scale Discovery multiplex assay. Mixed-sex APOE4 PMA were found to have higher basal messenger RNA expression of several pro-inflammatory cytokines including <i>Il6</i>, <i>Tnfa</i>, <i>Il1b</i>, <i>Mcp1</i>, <i>Mip1a</i>, and <i>Nos2</i> compared to APOE3 PMA, which was accompanied by increased levels of these secreted cytokines. In sex-specific cultures, basal expression of <i>Il1b</i>, <i>Il6</i>, and <i>Nos2</i> was 1.5 to 2.5 fold higher in APOE4 female PMA compared to APOE4 males, with both being higher than APOE3 PMA. Similar results were found for secreted levels of these cytokines. Together, these findings indicate that APOE4 genotype and female sex, contribute to a greater inflammatory response in primary astrocytes and these data may provide a framework for investigating the mechanisms contributing to genotype and sex differences in AD-related neuroinflammation.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914221144549"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/06/10.1177_17590914221144549.PMC9982390.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926145","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":"Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease.","authors":"Jinjing Jia,&nbsp;Jiayi Yin,&nbsp;Yu Zhang,&nbsp;Guangtao Xu,&nbsp;Min Wang,&nbsp;Haiying Jiang,&nbsp;Li Li,&nbsp;Xiansi Zeng,&nbsp;Dongsheng Zhu","doi":"10.1177/17590914231159226","DOIUrl":"https://doi.org/10.1177/17590914231159226","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common neurodegenerative disease. Increasing studies suggest that mitochondrial dysfunction is closely related to the pathogenesis of AD. Thioredoxin-1 (Trx-1), one of the major redox proteins in mammalian cells, plays neuroprotection in AD. However, whether Trx-1 could regulate the mitochondrial biogenesis in AD is largely unknown. In the present study, we found that Aβ_25-35 treatment not only markedly induced excessive production of reactive oxygen species and apoptosis, but also significantly decreased the number of mitochondria with biological activity and the adenosine triphosphate content in mitochondria, suggesting mitochondrial biogenesis was impaired in AD cells. These changes were reversed by Lentivirus-mediated stable overexpression of Trx-1 or exogenous administration of recombinant human Trx-1. What's more, adeno-associated virus-mediated specific overexpression of Trx-1 in the hippocampus of β-amyloid precursor protein/presenilin 1 (APP/PS1) mice ameliorated the learning and memory and attenuated hippocampal Aβ deposition. Importantly, overexpression of Trx-1 in APP/PS1 mice restored the decrease in mitochondrial biogenesis-associated proteins, including adenosine monophosphate -activated protein kinase (AMPK), silent information regulator factor 2-related enzyme 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). In addition, Lentivirus-mediated overexpression of Trx-1 in rat adrenal pheochromocytoma (PC12) cells also restored the decrease of AMPK, Sirt1, and PGC1α by Aβ_25-35 treatment. Pharmacological inhibition of AMPK activity significantly abolished the effect of Trx-1 on mitochondrial biogenesis. Taken together, our data provide evidence that Trx-1 promoted mitochondrial biogenesis via restoring AMPK/Sirt1/PGC1α pathway in AD.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231159226"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/d8/10.1177_17590914231159226.PMC9969465.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800043","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":"An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis.","authors":"Intakhar Ahmad, Stig Wergeland, Eystein Oveland, Lars Bø","doi":"10.1177/17590914231198980","DOIUrl":"10.1177/17590914231198980","url":null,"abstract":"<p><p>Elevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone model in mice (CPZ), a model of toxic/metabolic demyelination and remyelination in different brain areas. In MS gray matter (GM), CHI3L1 was detected primarily in astrocytes and in a subset of pyramidal neurons. In neurons, CHI3L1 immunopositivity was associated with lipofuscin-like substance accumulation, a sign of cellular aging that can lead to cell death. The density of CHI3L1-positive neurons was found to be significantly higher in normal-appearing MS GM tissue compared to that of control subjects (<i>p</i>  =  .014). In MS white matter (WM), CHI3L1 was detected in astrocytes located within lesion areas, as well as in perivascular normal-appearing areas and in phagocytic cells from the initial phases of lesion development. In the CPZ model, the density of CHI3L1-positive cells was strongly associated with microglial activation in the WM and choroid plexus inflammation. Compared to controls, CHI3L1 immunopositivity in WM was increased from an early phase of CPZ exposure. In the GM, CHI3L1 immunopositivity increased later in the CPZ exposure phase, particularly in the deep GM region. These results indicate that CHI3L1 is associated with neuronal deterioration, pre-lesion pathology, along with inflammation in MS.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231198980"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795761","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":"Casein Kinase 2 Mediates HIV- and Opioid-Induced Pathologic Phosphorylation of TAR DNA Binding Protein 43 in the Basal Ganglia.","authors":"Michael Ohene-Nyako, Sara R Nass, Hope T Richard, Robert Lukande, Melanie R Nicol, MaryPeace McRae, Pamela E Knapp, Kurt F Hauser","doi":"10.1177/17590914231158218","DOIUrl":"10.1177/17590914231158218","url":null,"abstract":"<p><strong>Summary statement: </strong>HIV/HIV-1 Tat and morphine independently increase pathologic phosphorylation of TAR DNA binding protein 43 in the striatum. HIV- and opioid-induced pathologic phosphorylation of TAR DNA binding protein 43 may involve enhanced CK2 activity and protein levels.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231158218"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/3a/10.1177_17590914231158218.PMC9998424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868374","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":"Neuroprotection by Preconditioning in Mice is Dependent on MyD88-Mediated CXCL10 Expression in Endothelial Cells.","authors":"Zhihong Chen,&nbsp;Weiwei Hu,&nbsp;Mynor J Mendez,&nbsp;Zachary C Gossman,&nbsp;Anthony Chomyk,&nbsp;Brendan T Boylan,&nbsp;Grahame J Kidd,&nbsp;Timothy W Phares,&nbsp;Cornelia C Bergmann,&nbsp;Bruce D Trapp","doi":"10.1177/17590914221146365","DOIUrl":"10.1177/17590914221146365","url":null,"abstract":"<p><p>The central nervous system (CNS) can be preconditioned to resist damage by peripheral pretreatment with low-dose gram-negative bacterial endotoxin lipopolysaccharide (LPS). Underlying mechanisms associated with transient protection of the cerebral cortex against traumatic brain injury include increased neuronal production of antiapoptotic and neurotrophic molecules, microglial-mediated displacement of inhibitory presynaptic terminals innervating the soma of cortical projection neurons, and synchronized firing of cortical projection neurons. However, the cell types and signaling responsible for these neuronal and microglial changes are unknown. A fundamental question is whether LPS penetrates the CNS or acts on the luminal surface of brain endothelial cells, thereby triggering an indirect parenchymal neuroprotective response. The present study shows that a low-dose intraperitoneal LPS treatment increases brain endothelial cell activation markers CD54, but does not open the blood-brain barrier or alter brain endothelial cell tight junctions as assessed by electron microscopy. NanoString nCounter transcript analyses of CD31-positive brain endothelial cells further revealed significant upregulation of <i>Cxcl10, C3, Ccl2, Il1β, Cxcl2,</i> and <i>Cxcl1</i>, consistent with identification of myeloid differentiation primary response 88 (MyD88) as a regulator of these transcripts by pathway analysis. Conditional genetic endothelial cell gene ablation approaches demonstrated that both MyD88-dependent Toll-like receptor 4 (TLR4) signaling and <i>Cxcl10</i> expression are essential for LPS-induced neuroprotection and microglial activation. These results suggest that C-X-C motif chemokine ligand 10 (CXCL10) production by endothelial cells in response to circulating TLR ligands may directly or indirectly signal to CXCR3 on neurons and/or microglia. Targeted activation of brain endothelial receptors may thus provide an attractive approach for inducing transient neuroprotection.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914221146365"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/50/10.1177_17590914221146365.PMC9810995.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211960","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":"Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice.","authors":"Takuya Kawamura, Gagandeep Singh Mallah, Maryam Ardalan, Tetyana Chumak, Pernilla Svedin, Lina Jonsson, Seyedeh Marziyeh Jabbari Shiadeh, Fanny Goretta, Tomoaki Ikeda, Henrik Hagberg, Mats Sandberg, Carina Mallard","doi":"10.1177/17590914231198983","DOIUrl":"10.1177/17590914231198983","url":null,"abstract":"<p><strong>Summary statement: </strong>Neonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD⁺) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD⁺ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231198983"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105321","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":"Transferrin Enhances Neuronal Differentiation.","authors":"María Julia Pérez,&nbsp;Tomas Roberto Carden,&nbsp;Paula Ayelen Dos Santos Claro,&nbsp;Susana Silberstein,&nbsp;Pablo Martin Páez,&nbsp;Veronica Teresita Cheli,&nbsp;Jorge Correale,&nbsp;Juana M Pasquini","doi":"10.1177/17590914231170703","DOIUrl":"https://doi.org/10.1177/17590914231170703","url":null,"abstract":"<p><p>Although transferrin (Tf) is a glycoprotein best known for its role in iron delivery, iron-independent functions have also been reported. Here, we assessed apoTf (aTf) treatment effects on Neuro-2a (N2a) cells, a mouse neuroblastoma cell line which, once differentiated, shares many properties with neurons, including process outgrowth, expression of selective neuronal markers, and electrical activity. We first examined the binding of Tf to its receptor (TfR) in our model and verified that, like neurons, N2a cells can internalize Tf from the culture medium. Next, studies on neuronal developmental parameters showed that Tf increases N2a survival through a decrease in apoptosis. Additionally, Tf accelerated the morphological development of N2a cells by promoting neurite outgrowth. These pro-differentiating effects were also observed in primary cultures of mouse cortical neurons treated with aTf, as neurons matured at a higher rate than controls and showed a decrease in the expression of early neuronal markers. Further experiments in iron-enriched and iron-deficient media showed that Tf preserved its pro-differentiation properties in N2a cells, with results hinting at a modulatory role for iron. Moreover, N2a-microglia co-cultures revealed an increase in IL-10 upon aTf treatment, which may be thought to favor N2a differentiation. Taken together, these findings suggest that Tf reduces cell death and favors the neuronal differentiation process, thus making Tf a promising candidate to be used in regenerative strategies for neurodegenerative diseases.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231170703"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/6f/10.1177_17590914231170703.PMC10134178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507415","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":"Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline.","authors":"G C Nascimento,&nbsp;M Bortolanza,&nbsp;A Bribian,&nbsp;G C Leal-Luiz,&nbsp;R Raisman-Vozari,&nbsp;L López-Mascaraque,&nbsp;E Del-Bel","doi":"10.1177/17590914231155976","DOIUrl":"https://doi.org/10.1177/17590914231155976","url":null,"abstract":"<p><strong>Summary statement: </strong>NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231155976"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/1f/10.1177_17590914231155976.PMC10084551.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9566783","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":"Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro","authors":"M. Dragić, Katarina Mihajlović, Marija Adzic, Marija Jakovljevic, M. Z. Kontić, N. Mitrović, Danijela Laketa, I. Lavrnja, M. Kipp, I. Grković, N. Nedeljkovic","doi":"10.1177/17590914221102068","DOIUrl":"https://doi.org/10.1177/17590914221102068","url":null,"abstract":"Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regulation of NTPDase2 by inflammatory mediators in primary astrocytes and oligodendroglial cell line OLN93. In physiological conditions, NTPDase2 protein was most abundant in the hippocampus, where it was found in fibrous astrocytes and synaptic endings in the synaptic-rich hippocampal layers. In TMT-induced neurodegeneration, NTPDase2-mRNA acutely decreased at 2-dpi and then gradually recovered to the control level at 7-dpi and 21-dpi. As determined by immunohistochemistry and double immunofluorescence, the decrease was most pronounced in the dentate gyrus (DG), where NTPDase2 withdrew from the synaptic boutons in the polymorphic layer of DG, whereas the recovery of the expression was most profound in the subgranular layer. Concerning the regulation of NTPDase2 gene expression, proinflammatory cytokines IL-6, IL-1β, TNFα, and IFNγ negatively regulated the expression of NTPDase2 in OLN93 cells, while did not altering the expression in primary astrocytes. Different cell-intrinsic stressors, such as depletion of intracellular energy store, oxidative stress, endoplasmic reticulum stress, and activation of protein kinase C, also massively disturbed the expression of the NTPDase2 gene. Together, our results suggest that the expression and the activity of NTPDase2 transiently cease in neurodegeneration and brain injury, most likely as a part of the acute adaptive response designed to promote cell defense, survival, and recovery.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46001693","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}