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A systematic review of the role of TREM2 in Alzheimer’s disease

中华医学杂志(英文版) 2024年第14期137卷 1684-1694页

作者： Yin Yunsi Yang Hanchen Li Ruiyang Wu Guangshan Qin Qi Tang Yi department of neurology & Innovation center for Neurological disorders Xuanwu Hospital Capital Medical University National Center for Neurological Disorders Beijing China

Background: Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from bothin vivo andin vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of ***: PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of ***: A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection ***: This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.

关键词： TREM2 Alzheimer’s disease Mouse model Microglia Amyloid-β accumulation Tau pathology Inflammation

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Enhancing the understanding between exercise and brain health:A new tool of oxygen imaging

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Journal of Sport and Health Science 2024年第6期13卷 751-752页

作者： Zhibo Wang Jianping Jia Innovation center for Neurological disorders and department of neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Oxygen is pivotal for brain metabolism,1 and understanding its dynamics within the cerebral cortex is essential for both fundamental neuroscience and clinical ***,Beinlich et al.2 introduced a novel tool,the Green enhanced Nano-lantern(GeNL),a bioluminescent oxygen sensor that allows for the real-time,high-resolution monitoring of oxygen distribution in the living mouse cerebral cortex.

关键词： metabolism cerebral al.

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Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

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Neural Regeneration Research 2024年第8期19卷 1651-1652页

作者： Manuel Bange Damian Marc Herz Dumitru Ciolac Gabriel Gonzalez-Escamilla Sergiu Groppa Section of Movement disorders and Neurostimulation Department of NeurologyFocus Program Translational Neuroscience(FTN)University Medical Center of the Johannes Gutenberg-University MainzMainzGermany

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement *** pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain *** r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

关键词： alterations movement

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Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： Daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

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Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

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Neural Regeneration Research 2024年第7期19卷 1532-1540页

作者： Qin Huang Minping Wei Xianjing Feng Yunfang Luo Yunhai Liu Jian Xia department of neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of neurology Peking University People’s HospitalBeijingChina Clinical Research center for Cerebrovascular Disease of Hunan Province Central South UniversityChangshaHunan ProvinceChina National Clinical Research center for Geriatric disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases *** of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation *** aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro *** observational retrospective study was *** May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy *** with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy *** gut microbiota was assessed through 16S ribosomal ribonucleic acid *** also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble *** observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy *** patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae *** lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation ***,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte ***,the role of the gut microbiota in hemorrhagic transformation was evaluated using

关键词： gut microbiota hemorrhagic transformation inflammation lipopolysaccharide stroke

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基层医疗机构失眠症诊断和治疗中国专家共识

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中华医学杂志 2024年第25期104卷 2296-2307页

作者：中国睡眠研究会 department of Psychiatry (sleep Medicine center) Nanfang Hospital Southern Medical University Guangzhou 510515 China

失眠症是最常见的睡眠障碍, 不仅增加多种躯体疾病和精神障碍的风险, 而且带来沉重的社会卫生经济学负担。然而目前国内外均缺乏针对基层医疗机构失眠症的诊疗规范。为此, 中国睡眠研究会组织国内睡眠医学专家, 以国内外最新的研究进展... 详细信息

失眠症是最常见的睡眠障碍, 不仅增加多种躯体疾病和精神障碍的风险, 而且带来沉重的社会卫生经济学负担。然而目前国内外均缺乏针对基层医疗机构失眠症的诊疗规范。为此, 中国睡眠研究会组织国内睡眠医学专家, 以国内外最新的研究进展为依据, 制订本专家共识, 针对失眠症的病理生理学机制、流行病学、诊断思路、筛查评估、防治措施和基层管理进行逐一阐述, 共制订了15条推荐意见, 以期为失眠症的基层医疗机构诊疗提供全面而规范的参考和建议。

关键词：睡眠障碍失眠症基层医疗机构专家共识诊断治疗

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The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

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Genes & Diseases 2024年第3期11卷 452-467页

作者： Min Wang Yixue Gu Qiubo Li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang department of neurology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China department of neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China department of Pediatrics Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China department of Neurosurgery Affliated Hospital of Jining Medical UniversityJiningShandong 272000China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent *** lobe epilepsy(TLE)is one of the most common medically intractable seizure ***2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains *** this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of ***(Co-IP)/mass spectrometry(MS)was used to identify the potential *** Co-IP,we detected and confirmed the main potential TNIK *** fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)*** found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with ***-0846 delayed kindling progression and decreased seizure ***-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably ***-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and *** addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ *** results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

关键词： Epilepsy NCB-0846 Rat TLE TNIK Traf2-and NcK-interacting kinase

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Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

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Neural Regeneration Research 2024年第12期19卷 2581-2582页

作者： Shuyu Zhang Paul Lingor department of neurology School of MedicineUniversity Hospital rechts der IsarTechnical University of MunichMunichGermany department of neurology University Medical Center GöttingenGöttingenGermany center for Biostructural Imaging of Neurodegeneration University Medical Center GöttingenGöttingenGermany

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) *** a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble *** forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

关键词： atrophy endogenous atypical

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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu department of neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics center National Clinical Research center for Geriatric disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key Laboratory of Hunan Province in Neurodegenerative disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

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Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

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General Psychiatry 2024年第1期37卷 53-63页

作者： Xingqi Wu Yibing Yan Panpan Hu Lu Wang Yue Wu Pan Wu Zhi Geng Guixian Xiao Shanshan Zhou Gongjun Ji Bensheng Qiu Ling Wei Yanghua Tian Hesheng Liu Kai Wang department of neurology First ffiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina School of Mental Health and Psychological Sciences Anhui Medical UniversityHefeiAnhuiChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric disorders HefeiAnhuiChina Collaborative Innovation center of Neuropsychiatric disorders and Mental Health HefeiAnhuiChina department of Psychology and sleep Medicine The Second Affliated Hospital of Anhui Medical UniversityHefeiAnhuiChina center for Biomedical Imaging University of Science and Technology of ChinaHefeiAnhuiChina institute of Artificial Intlligence Hefei Comprehensive National Science CenterHefeiAnhuiChina department of Neuroscience Medical University of South CarolinaCharlestonSouth CarolinaUSA

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for ***,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD *** We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with *** In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every *** included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the *** were evaluated at baseline and after *** longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over *** The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale *** baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at ***,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)*** D

关键词： stimulation Alzheimer maintained

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