{"title":"Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease","authors":"Arshad H. Khan, Lydia K. Lee, Desmond J. Smith","doi":"10.1101/2022.02.18.481079","DOIUrl":"https://doi.org/10.1101/2022.02.18.481079","url":null,"abstract":"Abstract Exposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15, and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"1 1","pages":"255 - 269"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82098840","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}
Zhen-Kun Gao, Xin-Ya Shen, Yu Han, Yi-Sha Guo, Kai Li, Xia Bi
{"title":"Pre-ischemic exercise prevents inflammation and apoptosis by inhibiting MAPK pathway in ischemic stroke.","authors":"Zhen-Kun Gao, Xin-Ya Shen, Yu Han, Yi-Sha Guo, Kai Li, Xia Bi","doi":"10.1515/tnsci-2022-0268","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0268","url":null,"abstract":"<p><strong>Introduction: </strong>Mitogen-activated protein kinase (MAPK) pathway is a major mechanism of acute brain damage in ischemic stroke. Pre-ischemic exercise is an effective method to reduce ischemic injury. However, the regulation by pre-ischemic exercise of MAPK pathway and associated mechanisms in animal models remains unclear.</p><p><strong>Materials and methods: </strong>In this study, Male SD rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group, and exercise plus MCAO (EX + MCAO) group for 21 days, and then was established by MCAO. Longa score was used to measure neurological deficits at 0, 1, 2, and 3 days after MCAO. Hematoxylin and eosin staining was used to observe the brain injury. The expression of MAPK pathway was quantified by western blot. The M1 microglia protein was quantified by western blot and immunofluorescence, and the level of inflammatory factor was measured by enzyme-linked immunosorbent assay. TUNEL staining and western blot were used to measure apoptosis.</p><p><strong>Results: </strong>In the current study, we observed that pre-ischemic exercise effectively decreased infarct volume, neurological deficit score and brain injury in MCAO rats through suppressing the activation of p-JNK and p-ERK1/2. Further investigation revealed that pre-ischemic exercise decreased M1 microglia activation and the serum level of TNF-α and IL-1β. In addition, the increased number of TUNEL-positive cells and Bax/Bcl-2 ratio also were reversed by pre-ischemic exercise.</p><p><strong>Conclusions: </strong>Pre-ischemic exercise can alleviate inflammatory response and apoptosis by inhibiting the MAPK pathway in MCAO rats.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"13 1","pages":"495-505"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9091802","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":"Mild acute stress prevents the memory impairment induced by long-term isoflurane anesthesia.","authors":"Tiantian Liu, Yutong Dai, Minhui Xu, Ying Chen, Tianjiao Xia, Xin Zhao","doi":"10.1515/tnsci-2022-0261","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0261","url":null,"abstract":"<p><strong>Objectives: </strong>Long-term isoflurane anesthesia exposure could result in postoperative cognitive dysfunction (POCD). Preoperative stress is also reported to be a risk factor of POCD. However, it is unknown whether acute stress could impair memory after long-term isoflurane anesthesia.</p><p><strong>Methods: </strong>In this study, we categorized the mice with acute stress into mild (30 min restraint stress), moderate (60 min restraint stress), and severe (120 min restraint stress) stress groups and then we used Open-Field Test (OFT) to detect whether different scales of acute restraint stress successfully induced acute stress in mice. The memory performance of mice was measured using contextual and cued memory test, and the brain-derived neurotrophic factor protein levels of hippocampus was detected by Western blot.</p><p><strong>Results: </strong>We verified that mild stress has pro-cognitive effect, but severe stress has amnestic effect. Moreover, we found that mild and moderate other than severe acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia.</p><p><strong>Conclusion: </strong>Mild and moderate acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"13 1","pages":"421-429"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10673642","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}
S. Afshar, S. Lule, Gengyang Yuan, Xiying Qu, C. Pan, M. Whalen, A. Brownell, M. Mody
{"title":"Longitudinal PET studies of mGluR5 in FXS using an FMR1 knockout mouse model","authors":"S. Afshar, S. Lule, Gengyang Yuan, Xiying Qu, C. Pan, M. Whalen, A. Brownell, M. Mody","doi":"10.1515/tnsci-2022-0217","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0217","url":null,"abstract":"Abstract Fragile X syndrome (FXS) is a monogenic disorder characterized by intellectual disability and behavioral challenges. It is caused by aberrant methylation of the fragile X mental retardation 1 (FMR1) gene. Given the failure of clinical trials in FXS and growing evidence of a role of metabotropic glutamate subtype 5 receptors (mGluR5) in the pathophysiology of the disorder, we investigated mGluR5 function in FMR1 Knockout (FMR1-KO) mice and age- and sex-matched control mice using longitudinal positron emission tomography (PET) imaging to better understand the disorder. The studies were repeated at four time points to examine age- and disease-induced changes in mGluR5 availability using 3-fluoro-[18F]5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB). We found that the binding potential (BP) of [18F]FPEB was significantly lower in the KO mice in mGluR5-implicated brain areas including striatum, cortex, hippocampus, thalamus, and olfactory bulb. The BP also changed with age, regardless of disorder status, increasing in early adulthood in male but not in female mice before decreasing later in both sexes. The difference in mGluR5 availability between the FMR1-KO and control mice and the change in BP in the KO mice as a function of age and sex illustrate the nature of the disorder and its progression, providing mechanistic insights for treatment design.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"89 1","pages":"80 - 92"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73639772","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}
Auwal Abdullahi, Bishir Sabo, Umaru Muhammad Badaru, Wim Saeys, Steven Truijen
{"title":"Factors influencing recovery of upper limb motor function during constraint-induced movement therapy for people with stroke.","authors":"Auwal Abdullahi, Bishir Sabo, Umaru Muhammad Badaru, Wim Saeys, Steven Truijen","doi":"10.1515/tnsci-2022-0260","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0260","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to determine the personal and clinical factors that can predict recovery of motor function in people with stroke.</p><p><strong>Methods: </strong>Characteristics of the study participants such as age, sex, time since stroke and type of stroke, motor function, shoulder pain, amount and quality of use of the affected limb in the real world, wrist and elbow spasticity, handedness, central post-stroke pain and dose of massed practice were recorded. The data obtained were analyzed using descriptive statistics and multiple regression.</p><p><strong>Results: </strong>A total of 144 patients with stroke with mean age, 58.71 ± 19.90 years participated in the study. The result showed that, the whole model significantly explained the total variance by 88.4%, <i>F</i>(14, 144) = 32.870, <i>R</i> <sup>2</sup> = 0. 0.781, <i>p</i> < 0.001. However, in the final model, only four independent variables in the order of degree of predictability, amount of use of the limb in the real world (Beta = 0.455, <i>p</i> = 0.003), intensity of practice during rehabilitation session (Beta = 0.321, <i>p</i> < 0.001), wrist spasticity (Beta = 0.148, <i>p</i> = 0.004) and side affected (Beta = 0.093, <i>p</i> = 0.033) significantly predicted recovery of motor function.</p><p><strong>Conclusion: </strong>Encouraging the use of the limb in the real world may be more important than practice during rehabilitation session in the clinic or in the laboratory.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"13 1","pages":"453-459"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9743202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10421518","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}
Soyeon Jun, Yihyun Joo, Youjin Sim, Chuyun Pyo, Keunsoo Ham
{"title":"Fronto-parietal single-trial brain connectivity benefits successful memory recognition.","authors":"Soyeon Jun, Yihyun Joo, Youjin Sim, Chuyun Pyo, Keunsoo Ham","doi":"10.1515/tnsci-2022-0265","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0265","url":null,"abstract":"Abstract Successful recognition has been known to produce distinct patterns of neural activity. Many studies have used spectral power or event-related potentials of single recognition-specific regions as classification features. However, this does not accurately reflect the mechanisms behind recognition, in that recognition requires multiple brain regions to work together. Hence, classification accuracy of subsequent memory performance could be improved by using functional connectivity within memory-related brain networks instead of using local brain activity as classifiers. In this study, we examined electroencephalography (EEG) signals while performing a word recognition memory task. Recorded EEG signals were collected using a 32-channel cap. Connectivity measures related to the left hemispheric fronto-parietal connectivity (P3 and F3) were found to contribute to the accurate recognition of previously studied memory items. Classification of subsequent memory outcome using connectivity features revealed that the classifier with support vector machine achieved the highest classification accuracy of 86.79 ± 5.93% (mean ± standard deviation) by using theta (3–8 Hz) connectivity during successful recognition trials. The results strongly suggest that highly accurate classification of subsequent memory outcome can be achieved by using single-trial functional connectivity.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"13 1","pages":"506-513"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553677","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":"Brain and gut microbiota disorders in the psychopathology of anorexia nervosa.","authors":"Mercedes Garcia-Gil, Maria Rachele Ceccarini, Fabrizio Stoppini, Samuela Cataldi, Claudia Mazzeschi, Elisa Delvecchio, Elisabetta Albi, Giulia Gizzi","doi":"10.1515/tnsci-2022-0267","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0267","url":null,"abstract":"<p><p>Studies of pathophysiological mechanisms involved in eating disorders (EDs) have intensified over the past several years, revealing their unprecedented and unanticipated complexity. Results from many articles highlight critical aspects in each member of ED family. Notably, anorexia nervosa (AN) is a disorder due to undefined etiology, frequently associated with symptoms of depression, anxiety, obsessive-compulsiveness, accompanied by endocrine alterations, altered immune response, increased inflammation, and dysbiosis of the gut microbiota. Hence, an advanced knowledge of how and why a multisystem involvement exists is of paramount importance to understand the pathogenetic mechanisms of AN. In this review, we describe the change in the brain structure/function focusing on hypothalamic endocrine disorders and the disequilibrium of gut microbiota in AN that might be responsible for the psychopathological complication.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"13 1","pages":"516-526"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10558620","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}
Z. Mai, Wenyan Wei, Haibing Yu, Yongze Chen, Yongxiang Wang, Yuanlin Ding
{"title":"Molecular recognition of the interaction between ApoE and the TREM2 protein","authors":"Z. Mai, Wenyan Wei, Haibing Yu, Yongze Chen, Yongxiang Wang, Yuanlin Ding","doi":"10.1515/tnsci-2022-0218","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0218","url":null,"abstract":"Abstract Alzheimer’s disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E (ApoE) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE. Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE–TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"93 - 103"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89803098","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}
Z. Wenbin, Huang Yeqing, Liu Aiqun, Hong Mingfan, Wei Zhisheng
{"title":"A rare giant intracranial arachnoid cyst confused the diagnosis and treatment of Wilson disease","authors":"Z. Wenbin, Huang Yeqing, Liu Aiqun, Hong Mingfan, Wei Zhisheng","doi":"10.1515/tnsci-2022-0213","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0213","url":null,"abstract":"Abstract Background Hepatolenticular degeneration (HLD), also known as Wilson disease (WD), is a rare autosomal-recessive hereditary disease, which is often missed and misdiagnosed because of its various clinical manifestations. And WD is even more rare with giant subarachnoid cysts. In this report, we will provide a case of WD with an intracranial arachnoid cyst (IAC). Case description A 27-year-old woman was hospitalized in a traditional Chinese medicine hospital in Guangzhou with the first manifestation of a “slight involuntary tremor of her left upper limb”. There was no improvement after acupuncture treatment, and then she was transferred to another large general hospital in Guangzhou. MRI examination of the head showed “left frontal, parietal and temporal giant subarachnoid cyst” and the patient underwent “left frontotemporal arachnoid cyst celiac shunt operation.” After the operation, the patient’s left limb shaking remained unchanged. Subsequently, the patient was referred to another big hospital in Guangzhou, considered “Parkinson’s disease,” and given “Medopa, Antan” and other treatments. However, the patient’s limb shaking continued to increase and gradually developed to the extremities. At last, the patient was referred to our hospital, combined with the medical history, neurological signs, and auxiliary examination results, improve the examination of corneal K-F ring, blood ceruloplasmin, gene screening, and other tests; the diagnosis was confirmed as hepatolenticular degeneration. Conclusion After expelling copper and symptomatic treatment, the condition is improved.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"53 1","pages":"52 - 56"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85078498","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":"Ischemic stroke following STA–MCA double bypass","authors":"Haijun Zhao, Xiaoguang Tong, Xu Wang, Maohua Ding, Kaiwen Zhang","doi":"10.1515/tnsci-2022-0211","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0211","url":null,"abstract":"Abstract Objectives The surgical technique of STA–MCA double bypass is used to improve blood flow supplied by the distal middle cerebral artery (MCA) to the cerebral territory. This retrospective study from a single center aimed to compare the outcomes following STA–MCA double bypass in 12 patients with recurrent ischemic stroke. Materials and methods We retrospectively analyzed the data from patients with internal carotid artery occlusion (ICAO) who had undergone STA–MCA double bypass in our center from January 2016 to December 2020. The surgical indications, evaluation of circle of Willis (CoW), changes in cerebral hemodynamic, surgical results, and follow-up results were analyzed. Results Post-operative perfusion-weighted imaging showed hemodynamic improvement in all 12 patients. Ten patients (83.33%) showed clinical improvement, and 2 patients (16.67%) had stable disease. No intracranial infections or acute ischemic events occurred. The post-operative National Institutes of Health Stroke Scale score and modified Barther scores were significantly improved after 180 days of follow-up. Twenty three (96%) anastomoses maintain patency of their bypass vessels, and none had recurrent cerebral infarction during a minimum of 36 months follow-up. Conclusion In this small study, in patients with recurrent ischemic stroke without other types of treatment, STA–MCA double bypass surgery was more effective in the subgroup of patients with ICAO and poor blood supply to the CoW and an area of cerebral hypoperfusion that exceeded the area supplied by the MCA.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"7 1","pages":"20 - 29"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82355006","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}