Experimental Neurology最新文献

{"title":"Combined biomaterial scaffold and neuromodulation strategy to promote tissue repair and corticospinal connectivity after spinal cord injury in a rodent model","authors":"P.T.J.A. Williams ,&nbsp;Eva Schelbaum ,&nbsp;Chaimae Ahmanna ,&nbsp;Heather Alexander ,&nbsp;Kadia Kanté ,&nbsp;Sylvia Soares ,&nbsp;Hisham Sharif ,&nbsp;Fatiha Nothias ,&nbsp;John H. Martin","doi":"10.1016/j.expneurol.2024.114965","DOIUrl":"10.1016/j.expneurol.2024.114965","url":null,"abstract":"<div><div>Spinal cord injury (SCI) damages the trauma site, leading to progressive and secondary structural defects rostral and caudal to the injury. Interruption of ascending and descending pathways produce motor, sensory, and autonomic impairments, driving the need for effective therapies. In this study, we address lesion site repair and promoting descending projections using a combined biomaterial-neuromodulation strategy in a rat model of cervical contusion SCI. To promote tissue repair, we used Chitosan fragmented physical hydrogel suspension (C_fphs), a biomaterial formulation optimized to mitigate inflammation and support tissue remodeling. To promote descending projections, we targeted the corticospinal motor system with dual motor cortex–trans-spinal direct current neuromodulation to promote spared corticospinal tract (CST) axon sprouting rostral and caudal to SCI. C_fphs, injected into the lesion site acutely, was followed by 10 days of daily neuromodulation. Analysis was made at the chronic phase, 8-weeks post-SCI. Compared with SCI only, C_fphs alone or in combination with neuromodulation prevented cavity formation, by promoting tissue remodeling at the injury site, abrogated astrogliosis surrounding the newly formed tissue, and enabled limited CST axon growth into the remodeled injury site. C_fphs alone significantly reduced CST axon dieback and was accompanied by preserving more CST axon gray matter projections rostral to SCI. C_fphs + neuromodulation produced sprouting rostral and caudal to injury. Our findings show that our novel biomaterial-neuromodulation combinatorial strategy achieves significant injury site tissue remodeling and promoted CST projections rostral and caudal to SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The beneficial effects of modafinil administration on repeat mild traumatic brain injury (RmTBI) pathology in adolescent male rats are not dependent upon the orexinergic system","authors":"Jennaya Christensen ,&nbsp;Elaina Vlassopoulos ,&nbsp;Christopher K. Barlow ,&nbsp;Ralf B. Schittenhelm ,&nbsp;Crystal N. Li ,&nbsp;Marissa Sgro ,&nbsp;Samantha Warren ,&nbsp;Bridgette D. Semple ,&nbsp;Glenn R. Yamakawa ,&nbsp;Sandy R. Shultz ,&nbsp;Richelle Mychasiuk","doi":"10.1016/j.expneurol.2024.114969","DOIUrl":"10.1016/j.expneurol.2024.114969","url":null,"abstract":"<div><div>The sleep-wake cycle plays an influential role in the development and progression of repeat mild traumatic brain injury (RmTBI)-related pathology. Therefore, we first aimed to manipulate the sleep-wake cycle post-RmTBI using modafinil, a wake-promoting substance used for the treatment of narcolepsy. We hypothesized that modafinil would exacerbate RmTBI-induced deficits. Chronic behavioural analyses were completed along with a 27-plex serum cytokine array, metabolomic and proteomic analyses of cerebrospinal fluid (CSF), as well as immunohistochemical staining in structures important for sleep/wake cycles, to examine orexin, melanin-concentrating hormone, tyrosine hydroxylase, and choline acetyltransferase, in the lateral hypothalamus, locus coeruleus, and basal forebrain, respectively. Contrary to expectation, modafinil administration attenuated behavioural deficits, metabolomic changes, and neuropathological modifications. Therefore, the second aim was to determine if the beneficial effects of modafinil treatment were driven by the orexinergic system. The same experimental protocol was used; however, RmTBI rats received chronic orexin-A administration instead of modafinil. Orexin-A administration produced drastically different outcomes, exacerbating anxiety-related and motor deficits, while also significantly disrupting their metabolomic and neuropathological profiles. These results suggest that the beneficial effects of modafinil administration post-RmTBI, work independently of its wake-promoting properties, as activation of the orexinergic wake-promoting system with orexin-A was detrimental. Overall, these findings highlight the complexity of sleep-wake changes in the injured brain and showcase the potential of the arousal and sleep systems in its treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain","authors":"Peyton Grace Howard ,&nbsp;Peibin Zou ,&nbsp;Yulan Zhang ,&nbsp;Fang Huang ,&nbsp;Vesna Tesic ,&nbsp;Celeste Yin-Chieh Wu ,&nbsp;Reggie Hui-Chao Lee","doi":"10.1016/j.expneurol.2024.114973","DOIUrl":"10.1016/j.expneurol.2024.114973","url":null,"abstract":"<div><div>Serum/Glucocorticoid Regulated Kinase 1 (SGK1), a serine/threonine kinase, is ubiquitous across a wide range of tissues, orchestrating numerous signaling pathways and associated with various human diseases. SGK1 has been extensively explored in diverse types of immune and inflammatory diseases, cardiovascular disorders, as well as cancer metastasis. These studies link SGK1 to cellular proliferation, survival, metabolism, membrane transport, and drug resistance. Recently, increasing research has focused on SGK1's role in neurological disorders, including a variety of neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease and Parkinson's disease), brain injuries (e.g., cerebral ischemia and traumatic brain injury), psychiatric conditions (e.g., depression and drug addiction). SGK1 is emerging as an increasingly compelling therapeutic target across the spectrum of neurological disorders, supported by the availability of several effective agents. However, the conclusions of many studies observing the prevalence and function of SGK1 in neurological disorders are contradictory, necessitating a review of the SGK1 research within neurological disorders. Herein, we review recent literature on SGK1's primary functions within the nervous system and its impacts within different neurological disorders. We summarize significant findings, identify research gaps, and outline possible future research directions based on the current understanding of SGK1 to help further progress the understanding and treatment of neurological disorders.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGN-020 ameliorates motor dysfunction post-spinal cord injury via enhancing astrocyte autophagy and mitigating inflammation by activating AQP4/PPAR-γ/mTOR pathway","authors":"Jundong Kong ,&nbsp;Qiangqiang Zhang ,&nbsp;Haohong Zheng ,&nbsp;Diandong Tang ,&nbsp;Li Fang ,&nbsp;Shuaihao An ,&nbsp;Jian Li ,&nbsp;Zhongkai Fan","doi":"10.1016/j.expneurol.2024.114975","DOIUrl":"10.1016/j.expneurol.2024.114975","url":null,"abstract":"<div><div>Spinal Cord Injury (SCI) is a severe condition that often leads to substantial neurological impairments. This study aimed to explore the role of Aquaporin-4 (AQP4) in regulating astrocyte autophagy and neuroinflammation post-SCI, as well as to evaluate the therapeutic potential of AQP4 inhibition using the specific inhibitor TGN-020. Using Western blot, CCK8 assays, immunofluorescence staining, histopathological assessments, and behavioral analyses, we investigated the effects of TGN-020 on SCI-induced alterations in autophagy, neuroinflammation, astrocyte proliferation, neuronal damage, and motor function recovery in both rat and astrocyte models. Our findings indicate that TGN-020 significantly enhances astrocyte autophagy, reduces neuroinflammation, thereby leading to mitigated astrocyte activation by suppressing AQP4 expression. These beneficial effects are associated with the activation of the peroxisome proliferator-activated receptor-γ/mammalian target of rapamycin (PPAR-γ/mTOR) signaling pathway. Notably, the introduction of the PPAR-γ specific inhibitor GW9662 abrogated the positive regulatory effects of TGN-020 on SCI-induced autophagy and neuroinflammation. Collectively, our in vivo and in vitro experiments demonstrate that TGN-020, by down-regulating AQP4, activates the PPAR-γ/mTOR pathway, ameliorates astrocyte autophagy, diminishes neuroinflammation, and ultimately enhances motor function recovery.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of key regulatory genes involved in myelination after spinal cord injury by GSEA analysis","authors":"Yehua Lv ,&nbsp;Lingyun Ji ,&nbsp;Hui Dai,&nbsp;Shanru Qiu,&nbsp;Yu Wang,&nbsp;Cheng Teng,&nbsp;Bin Yu,&nbsp;Daguo Mi,&nbsp;Chun Yao","doi":"10.1016/j.expneurol.2024.114966","DOIUrl":"10.1016/j.expneurol.2024.114966","url":null,"abstract":"<div><div>Multilayer dense myelin tissue provides insulating space and nutritional support for axons in healthy spinal cord tissue. Oligodendrocyte precursor cells (OPCs) are the main glial cells that complement myelin loss in the central nervous system and play an important role in the repair of spinal cord injury (SCI). However, the regulation of axonal remyelination after SCI is still insufficient. In this study, we focused on the changes in genes related to myelin repair after rat hemisection SCI by gene set enrichment analysis (GSEA). Key genes proteolipid protein 1 (Plp1), hexosaminidase subunit alpha (Hexa), and hexosaminidase subunit beta (Hexb) during remyelination after SCI were found. Through quantitative real-time polymerase chain reaction (qPCR) experiments, we confirmed that within 28 days after rat hemisection SCI, the mRNA expression of gene Plp1 gradually decreased, while the expressions of gene Hexa and Hexb gradually increased, which was consistent with RNA sequencing results. In vitro, we performed EdU proliferation assays on OPC cell line OLN-93 and primary rat OPCs. We found that interference of Plp1 promoted OPC proliferation, while interference of Hexa and Hexb inhibited OPC proliferation. In addition, we performed in vitro differentiation experiments on primary rat OPCs. By measuring myelin sheath branch outgrowth and the fluorescence intensity of the mature myelin sheath marker myelin basic protein (MBP), we found that interference of Hexa or Hexb promoted OPC differentiation and maturation, but interference of Plp1 inhibited this process. Finally, we injected Hexb siRNA in vivo and found that interfering Hexb could improve motor movements and myelin regeneration after SCI in rats. Our results provide new target genes that can selectively regulate the proliferation and differentiation of endogenous OPCs, providing new ideas for promoting remyelination and functional recovery after SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer RNAs and transfer RNA-derived small RNAs in cerebrovascular diseases","authors":"Jiajie Yuan ,&nbsp;Zibin Song ,&nbsp;Jun Liu ,&nbsp;Khalil Ur Rahman ,&nbsp;Qixiong Zhou ,&nbsp;Guangjie Liu ,&nbsp;Yifeng Deng ,&nbsp;Haotian Wen ,&nbsp;Xiaonan Fan ,&nbsp;Nanqi Fang ,&nbsp;Zhaojun Zhou ,&nbsp;Qiancheng Song ,&nbsp;Guozhong Zhang ,&nbsp;Peng Li ,&nbsp;Ye Song","doi":"10.1016/j.expneurol.2024.114971","DOIUrl":"10.1016/j.expneurol.2024.114971","url":null,"abstract":"<div><div>This article explores the important functions of transfer RNA and - transfer RNA derived small RNAs (tsRNAs) in cellular processes and disease pathogenesis, with a particular emphasis on their involvement in cerebrovascular disorders. It discusses the biogenesis and structure of tsRNAs, including types such as tRNA halves and tRNA-derived fragments, and their functional significance in gene regulation, stress response, and cell signaling pathways. The importance of tsRNAs in neurodegenerative diseases, cancer, and cardiovascular diseases has already been highlighted, while their role in cerebrovascular diseases is in early phase of exploration. This paper presents the latest advancements in the field of tsRNAs in cerebrovascular conditions, such as ischemic stroke, intracerebral hemorrhage, and moyamoya disease. Furthermore, revealing the aptitude of tsRNAs as biomarkers for the prediction of cerebrovascular diseases and as targets for therapeutic intervention. It provides insights into the role of tsRNAs in these conditions and proposes directions for future research.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common and divergent pathways in early stages of glutamate and tau-mediated toxicities in neurodegeneration","authors":"Anjalika Chongtham ,&nbsp;Abhijeet Sharma ,&nbsp;Banshi Nath ,&nbsp;Kaitlin Murtha ,&nbsp;Kirill Gorbachev ,&nbsp;Aarthi Ramakrishnan ,&nbsp;Eric F. Schmidt ,&nbsp;Li Shen ,&nbsp;Ana C. Pereira","doi":"10.1016/j.expneurol.2024.114967","DOIUrl":"10.1016/j.expneurol.2024.114967","url":null,"abstract":"<div><div>It has been shown that excitotoxicity and tau-mediated toxicities are major contributing factors to neuronal death in Alzheimer's disease (AD). The excitatory amino acid transporter 2 (EAAT2 or <em>GLT-1</em>), the major glutamate transporter in the brain that regulates glutamate levels synaptically and extrasynaptically, has been shown to be deficient in AD brains, leading to excitotoxicity and subsequent cell death. Similarly, buildup of neurofibrillary tangles, which consist of hyperphosphorylated tau protein, correlates with cognitive decline and neuronal atrophy in AD. However, common genes and pathways that are critical in the aforementioned toxicities have not been well elucidated. To investigate the impact of glutamate dyshomeostasis and tau accumulation on translational profiles of affected hippocampal neurons, we used mouse models of excitotoxicity and tau–mediated toxicities (<em>GLT-1</em>^−/− and P301S, respectively) in conjunction with BAC-TRAP technology. Our data show that GLT-1 deficiency in CA3 pyramidal neurons leads to translational signatures characterized by dysregulation of pathways associated with synaptic plasticity and neuronal survival, while the P301S mutation induces changes in endocytic pathways and mitochondrial dysfunction. Finally, the commonly dysregulated pathways include impaired ion homeostasis and metabolic pathways. These common pathways may shed light on potential therapeutic targets for ameliorating glutamate and tau-mediated toxicities in AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic SHQ1 variants result in disruptions to neuronal development and the dopaminergic pathway","authors":"Chien-Hui Chang ,&nbsp;Lee-Chin Wong ,&nbsp;Chia-Wei Huang ,&nbsp;Yue-Ru Li ,&nbsp;Chainne-Wen Yang ,&nbsp;Jin-Wu Tsai ,&nbsp;Wang-Tso Lee","doi":"10.1016/j.expneurol.2024.114968","DOIUrl":"10.1016/j.expneurol.2024.114968","url":null,"abstract":"<div><h3>Background</h3><div>Compound heterozygous variants of <em>SHQ1</em>, an assembly factor of H/ACA ribonucleoproteins (RNPs) involved in critical biological pathways, have been identified in patients with developmental delay, dystonia, epilepsy, and microcephaly. We investigated the role of SHQ1 in brain development and movement disorders.</div></div><div><h3>Methods</h3><div><em>SHQ1</em> expression was knocked down using short-hairpin RNA (shRNA) to investigate its effects on neurons. <em>Shq1</em> shRNA and cDNA of WT and mutant <em>SHQ1</em> were also introduced into neural progenitors in the embryonic mouse cortex through <em>in utero</em> electroporation. Co-immunoprecipitation was performed to investigate the interaction between SHQ1 and DKC1, a core protein of H/ACA RNPs.</div></div><div><h3>Results</h3><div>We found that SHQ1 was highly expressed in the developing mouse cortex. <em>SHQ1</em> knockdown impaired the migration and neurite morphology of cortical neurons during brain development. Additionally, <em>SHQ1</em> knockdown impaired neurite growth and sensitivity to glutamate toxicity <em>in vitro</em>. There was also increased dopaminergic function upon <em>SHQ1</em> knockdown, which may underlie the increased glutamate toxicity of the cells. Most SHQ1 variants attenuated their binding ability toward DKC1, implying <em>SHQ1</em> variants may influence brain development by disrupting the assembly and biogenesis of H/ACA RNPs.</div></div><div><h3>Conclusions</h3><div>SHQ1 plays an essential role in brain development and dopaminergic function by upregulating dopaminergic pathways and regulating the behaviors of neural progenitors and their neuronal progeny, potentially leading to dystonia and developmental delay in patients. Our study provides insights into the functions of SHQ1 in neuronal development and dopaminergic function, providing a possible pathogenic mechanism for H/ACA RNPs-related disorders.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative transcriptomic analysis reveals Cd72 as a novel pro-inflammatory factor in microglia following experimental ischemic stroke","authors":"Haojie Ding ,&nbsp;Xuan Shi ,&nbsp;Junwei Ma ,&nbsp;Chang Cao ,&nbsp;Yangyang Liu ,&nbsp;Jinxin Lu ,&nbsp;Lei Bai ,&nbsp;Xiang Li Jr ,&nbsp;Haiying Li","doi":"10.1016/j.expneurol.2024.114974","DOIUrl":"10.1016/j.expneurol.2024.114974","url":null,"abstract":"<div><div>Ischemic stroke remains a leading cause of global mortality and disability, with neuroinflammation playing a critical role in determining patient outcomes. Microglia, the brain's resident immune cells, can both exacerbate neuroinflammation and neuronal damage by releasing neurotoxic mediators and engaging in excessive phagocytosis, while also aiding recovery through the production of anti-inflammatory cytokines and debris clearance. However, the molecular mechanisms governing microglial activation and polarization after ischemic stroke are not well elucidated. In this study, we combined integrative transcriptomic analyses with experimental validation in a murine model of middle cerebral artery occlusion/reperfusion (MCAO/R) to explore microglial heterogeneity and identify key regulatory factors in ischemic stroke. Bioinformatics analysis identified Cd72 as a novel pro-inflammatory modulator within ischemia-associated microglial phenotypes. We observed significant upregulation of Cd72 in microglia following MCAO/R, and selective knockdown of Cd72 using CX3CR1^Cre/ERT2 mice and Cre recombinase-dependent adeno-associated virus reduced MCAO/R-induced infarct volume, neuronal apoptosis, and neurological deficits. Furthermore, Cd72 expression in microglia was positively correlated with pro-inflammatory pathways and cytokines, including TNF-α, IL-1β, and IL-6. Knockdown of Cd72 significantly reduced these pro-inflammatory factors, highlighting its potential as a therapeutic target for mitigating inflammation in ischemic stroke. In conclusion, this study identifies Cd72 as a critical pro-inflammatory regulator in microglia following ischemic stroke, with its knockdown effectively reducing neuroinflammation and associated brain injury, highlighting Cd72 as a promising therapeutic target.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion","authors":"Jiahui Liang ,&nbsp;Zhiyi Xiong ,&nbsp;Qingfeng Lei ,&nbsp;Zimu Jiang ,&nbsp;Jiating Wei ,&nbsp;Fubing Ouyang ,&nbsp;Yicong Chen ,&nbsp;Jinsheng Zeng","doi":"10.1016/j.expneurol.2024.114970","DOIUrl":"10.1016/j.expneurol.2024.114970","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.</div></div><div><h3>Methods</h3><div>Twenty adult male cynomolgus monkeys were divided into the sham (<em>n</em> = 4), middle cerebral artery occlusion (MCAO, <em>n</em> = 5), MCAO + FMT (<em>n</em> = 3), and donor (<em>n</em> = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.</div></div><div><h3>Results</h3><div>At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all <em>P</em> &lt; 0.05), lower relative abundance of <em>Lactobacillus</em> (all <em>P</em> &lt; 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all <em>P</em> &lt; 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both <em>P</em> &lt; 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, <em>P</em> &lt; 0.05) was higher in the MCAO+FMT group than in the MCAO group.</div></div><div><h3>Conclusions</h3><div>Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as <em>Lactobacillus,</em> GABA, and Gln in the CSF and can be ameliorated using FMT.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}