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Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-βand Prevents Alzheimer’s Disease-Type Pathology and Cognitive Deficits

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neuroscience Bulletin 2023年第12期39卷 1775-1788页

作者： Zhi-Hao Liu Yu-Di Bai Zhong-Yuan Yu Hui-Yun Li Jie Liu Cheng-Rong Tan Gui-Hua Zeng Yun-Feng Tu Pu-Yang Sun Yu-Juan Jia Jin-Cai He Yan-Jiang Wang Xian-Le Bu department of neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China department of neurology and centre for clinical neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China Institute of Brain and Intelligence Third Military Medical UniversityChongqing400042China State Key Laboratory of Trauma Burns and Combined InjuryThird Military Medical UniversityChongqing400042China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai201200China

Deficiencies in the clearance of peripheral amyloidβ(Aβ)play a crucial role in the progression of Alzheimer’s disease(AD).Previous studies have shown that the ability of blood monocytes to phagocytose Aβis decreased in AD.However,the exact mechanism of Aβclearance dysfunction in AD monocytes remains unclear.In the present study,we found that blood monocytes in AD mice exhibited decreases in energy metabolism,which was accompanied by cellular senescence,a senescence-associated secretory phenotype,and dysfunctional phagocytosis of Aβ.Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβin vivo and in vitro.Moreover,enhancing blood monocyte Aβphagocytosis by improving energy metabolism alleviated brain Aβdeposition and neuroinflammation and eventually improved cognitive function in AD mice.This study reveals a new mechanism of impaired Aβphagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

关键词： Alzheimer's disease Aβclearance Monocyte Phagocytosis Energy metabolism

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Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer’s Disease and Attenuate AD-type Pathology in a Mouse Model

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neuroscience Bulletin 2022年第9期38卷 1025-1040页

作者： Jie-Ming Jian Dong-Yu Fan Ding-Yuan Tian Yuan Cheng Pu-Yang Sun Cheng-Rong Tan Gui-Hua Zeng Chen-Yang He Ye-Ran Wang Jie Zhu Xiu-Qing Yao Yan-Jiang Wang Yu-Hui Liu department of neurology and centre for clinical neuroscience Daping HospitalThird Military Medical UniversityChongqing400000China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse857000China department of Rehabilitation the Second Affiliated Hospital of Chongqing Medical UniversityChongqing400000China Key Laboratory of Ageing and Brain Disease Chongqing400000China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai200031China

Increased neuronal apoptosis is an important pathological feature of Alzheimer’s disease(AD).The Bcl-2-interacting mediator of cell death(Bim)mediates amyloid-beta(Aβ)-induced neuronal apoptosis.Naturally-occurring antibodies against Bim(NAbs-Bim)exist in human blood,with their levels and functions unknown in AD.In this study,we found that circulating NAbs-Bim were decreased in AD patients.Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions.Furthermore,NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβdeposition,tau hyperphosphorylation,microgliosis,and neuronal apoptosis in APP/PS1 mice.In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein.These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.

关键词： Alzheimer’s disease Amyloid-beta Bim Naturally-occurring antibodies Neuronal apoptosis

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Solitary fibrous tumor of the renal pelvis:A case report

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World Journal of clinical Cases 2022年第27期10卷 9798-9804页

作者： Min Liu Chao Zheng Jin Wang Ji-Xue Wang Liang He department of Urology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina department of neurology and neuroscience Center The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND Solitary fibrous tumor(SFT)is a rare mesenchymal neoplasm.SFT derived from the renal pelvis is an exceedingly rare entity.In this study,we report a case of renal pelvis SFT and review the relevant literature on this rare tumor.CASE SUMMARY A 76-year-old man was hospitalized due to right lumbar and abdominal pain.Abdominal computed tomography showed a hypervascular space-occupying renal lesion,sized 2.3 cm×1.8 cm.Based on the computed tomography findings,the patient was diagnosed with right renal pelvis tumor and underwent nephrectomy.Postoperative immunohistochemical results confirmed the diagnosis.As of the 3-year follow-up,there were no signs of recurrence,and the patient has recovered well.CONCLUSION We report a rare case of SFT derived from the renal pelvis and discuss the imaging and histopathological features that distinguish renal pelvis SFT from other renal pelvis tumors.

关键词： Renal pelvis Solitary fibrous tumor Surgery Computed tomography Case report

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A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum

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Neural Regeneration Research 2023年第2期18卷 344-349页

作者： Li-Min Wang Zhi-Hua Liu Hong-Lei Ren Xue-Mei Chen Jun-Min Wang Hui-Min Cai Li-Ping Wei Hui-Hong Tian Jian Wang Li-Juan Wang The Second School of clinical Medicine Southern Medical UniversityGuangzhouGuangdong ProvinceChina department of neurology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangdong Neuroscience InstituteGuangzhouGuangdong ProvinceChina School of Medicine South China University of TechnologyGuangzhouGuangdong ProvinceChina department of neurology Tianjin Neurological InstituteTianjin Medical University General HospitalTianjinChina department of Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina

The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse models of ICH by injecting collagenaseⅦ-S into the left striatum.Twenty-one days later,we injected collagenaseⅦ-S into the right striatum to simulate recurrent ICH.Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage,delayed recovery in locomotor function,motor coordination,and movement speed,and more obvious emotional and cognitive dysfunction than mice subjected to unilate ral striatal hemorrhage.These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH.These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

关键词： animal model cognition impairment depression-like behavior dopaminergic neurons emotion intracerebral hemorrhage motor neurologic function recurrent intracerebral hemorrhage

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Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease

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neuroscience Bulletin 2023年第2期39卷 261-272页

作者： Chen-Yang He Ding-Yuan Tian Si-Han Chen Wang-Sheng Jin Yuan Cheng Jia-Yan Xin Wei-Wei Li Gui-Hua Zeng Cheng-Rong Tan Jie-Ming Jian Dong-Yu Fan Jun-Rong Ren Yu-Hui Liu Yan-Jiang Wang Fan Zeng department of neurology and Center for clinical neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China The Institute of Brain and Intelligence Third Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing 400042China State Key Laboratory of Trauma Burn and Combined InjuryDaping HospitalThird Military Medical UniversityChongqing 400042China department of Cardiology Southwest HospitalThird Military Medical UniversityChongqing 400042China department of neurology Nanchong Central HospitalThe Second Clinical Medical SchoolNorth Sichuan Medical CollegeNanchong 637000China department of clinical Medicine North Sichuan Medical CollegeNanchong 637000China department of neurology The General Hospital of Western Theater CommandChengdu 610000China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse 857000China

The extracellular domain(p75ECD)of p75 neurotrophin receptor(p75NTR)antagonizes Aβ neurotoxicity and promotes Aβclearance in Alzheimer’s disease(AD).The impaired shedding of p75ECD is a key pathological process in AD,but its regulatory mechanism is largely unknown.This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD(p75ECD-NAbs)in AD patients and their effects on AD pathology.We found that the cerebrospinal fluid(CSF)level of p75ECD-NAbs was increased in AD,and negatively associated with the CSF levels of p75ECD.Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain,as well as worse cognitive functions than the control groups,which were immunized with Re-p75ECD(the reverse sequence of p75ECD)and phosphate-buffered saline,respectively.These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance,providing a novel insight into the role of autoimmunity and p75NTR in AD.

关键词： Alzheimer’s disease p75 neurotrophin receptor Extracellular domain Autoantibody Amyloidbeta Immunity

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Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema

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慢性疾病与转化医学:英文版 2023年第3期9卷 258-262页

作者： Julia Feige Fritz Klausner Johannes A.R.Pfaff Eugen Trinka Slaven Pikija Mahdi Safdarian department of neurology Neurocritical Care and NeurorehabilitationCentre of Cognitive NeuroscienceChristian Doppler University HospitalParacelsus Medical UniversitySalzburgMember of EpiCARESalzburgAustria department of Neuroradiology Christian Doppler University HospitalParacelsus Medical UniversitySalzburgAustria neuroscience Institute Christian‐Doppler University HospitalParacelsus Medical UniversityCentre for Cognitive NeuroscienceSalzburgAustria Institute of Public Health Medical Decision‐Making and HTAUMIT‐Private University for Health SciencesMedical Informatics and TechnologyHall in TyrolAustria

1|INTRODUCTION Capecitabine is an oral prodrug of 5-fluorouracil(5-FU),which is widely used for adjuvant and neoadjuvant chemotherapy of different solid tumors,particularly breast and colorectal cancers.1 Neurotoxicity of capecitabine has been consistently reported as capecitabine-induced toxic leukoencephalopathy,which includes bilateral lesions in the corpus callosum and corticospinal tract presenting as acute or delayed central nervous system toxicity.2 This side effect requires discontinuation of chemotherapy3;however,neurological symptoms due to capecitabine are reported to be usually reversible upon drug withdrawal.

关键词： capecitabine intramyelinic edema leukoencephalopathy stroke

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Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebralβ-amyloid deposition and brain atrophy

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Chinese Medical Journal 2022年第5期135卷 591-597页

作者： Dongyu Fan Huiyun Li Dongwan Chen Yang Chen Xu Yi Heng Yang Qianqian Shi Fangyang Jiao Yi Tang Qiming Li Fangyang Wang Shunan Wang Rongbing Jin Fan Zeng Yanjiang Wang department of neurology and centre for clinical neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China Institute of Brain and Intelligence Third Military Medical UniversityChongqing400038China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityTibet 857012China department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing400042China department of Radiology Daping HospitalThird Military Medical UniversityChongqing400042China

Background:Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease(AD).However,there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology.We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.Methods:We enrolled a group of cognitively normal patients(median age:64 years)with unilateral chronic cerebral hypoperfusion.Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion.11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.Results:The median age of the 10 participants,consisting of 4 males and 6 females,was 64 years(47-76 years).We found that there were no differences in standard uptake ratios of the cortex(volume of interest[VOI]:P=0.721,region of interest[ROI]:P=0.241)and grey/white ratio(VOI:P=0.333,ROI:P=0.445)and brain atrophy indices(Bicaudate,Bifrontal,Evans,Cella,Cella media,and Ventricular index,P>0.05)between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.Conclusion:Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebralβ-amyloid deposition and neurodegeneration in humans.

关键词： Cerebral hypoperfusion β-amyloid Brain atrophy Alzheimer disease

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Abnormal characterization of dynamic functional connectivity in Alzheimer’s disease

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Neural Regeneration Research 2022年第9期17卷 2014-2021页

作者： Cui Zhao Wei-Jie Huang Feng Feng Bo Zhou Hong-Xiang Yao Yan-E Guo Pan Wang Lu-Ning Wang Ni Shu Xi Zhang department of neurology Second Medical CenterNational Clinical Research Center for Geriatric DiseaseChinese PLA General HospitalBeijingChina department of Geriatrics Affiliated Hospital of Chengde Medical UniversityChengdeHebei ProvinceChina State Key Laboratory of Cognitive neuroscience and Learning Beijing Normal UniversityBeijingChina Center for Collaboration and Innovation in Brain and Learning Sciences Beijing Normal UniversityBeijingChina Beijing Key Laboratory of Brain Imaging and Connectomics Beijing Normal UniversityBeijingChina department of neurology First Medical CenterChinese PLA General HospitalBeijingChina department of neurology PLA Rocket Force Characteristic Medical CenterBeijingChina department of Radiology Second Medical CenterChinese PLA General HospitalBeijingChina department of neurology Tianjin Huanhu HospitalTianjinChina

Numerous studies have shown abnormal brain functional connectivity in individuals with Alzheimer’s disease(AD)or amnestic mild cognitive impairment(aMCI).However,most studies examined traditional resting state functional connections,ignoring the instantaneous connection mode of the whole brain.In this case-control study,we used a new method called dynamic functional connectivity(DFC)to look for abnormalities in patients with AD and aMCI.We calculated dynamic functional connectivity strength from functional magnetic resonance imaging data for each participant,and then used a support vector machine to classify AD patients and normal controls.Finally,we highlighted brain regions and brain networks that made the largest contributions to the classification.We found differences in dynamic function connectivity strength in the left precuneus,default mode network,and dorsal attention network among normal controls,aMCI patients,and AD patients.These abnormalities are potential imaging markers for the early diagnosis of AD.

关键词： Alzheimer’s disease amnestic mild cognitive impairment blood oxygen level-dependent default mode network dynamic functional connectivity frontoparietal network resting-state functional magnetic resonance imaging support vector machine

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A New Perspective for Parkinson's Disease:Circadian Rhythm

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neuroscience Bulletin 2017年第1期33卷 62-72页

作者： Siyue Li Yali Wang Fen Wang Li-Fang Hu Chun-Feng Liu department of neurology and Suzhou clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University Institutes of neuroscience Soochow University

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei （SCN） in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson＇s disease （PD） exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative conse- quences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

关键词： Parkinson＇s disease Circadian rhythm Sleep Dopamine

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Differential Kinematic Encoding of Saccades and Smooth-pursuit Eye Movements by Fastigial Neurons

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neuroscience Bulletin 2022年第8期38卷 927-932页

作者： Zongpeng Sun Peter W.Dicke Peter Thier School of Psychology Shaanxi Normal UniversityXi’an710062China department of Cognitive neurology Hertie Institute for Clinical Brain Research72076TübingenGermany

Dear Editor,Saccades and smooth-pursuit eye movements(SPEMs)are two categories of eye movements with very different kinematics,in particular very different acceleration and velocity ranges,differences that have contributed to the notion of largely segregated underlying neuronal circuits.For instance,it has been suggested that distinct wellsegregated pools of oculomotor vermis(OMV)Purkinje cells(PCs)are specialized for the fine-tuning of the relevant kinematic parameters characterizing each of them.

关键词： pursuit specialized instance

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