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Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

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Neuroscience Bulletin 2010年第4期26卷 297-303页

作者：王姗姗闫雪波 Michel A.Hofman dick F.swaab 周江宁解放军总医院南楼神经内科北京100853 合肥微尺度物质科学国家实验室中国科学技术大学生命科学院神经生物学系合肥230027 荷兰皇家艺术与科学研究院神经科学研究所

Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to *** the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat *** The rats were exposed to one of the stressors each day for 21 *** was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in *** After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor ***,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by *** densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control *** The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.

关键词： chronic unpredictable mild stress hypothalamo-pituitary-adrenal axis corticotropin-releasing hormone amygdala paraventricular nucleus

Progress in Human Brain Banking in China

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Neuroscience Bulletin 2019年第2期35卷 179-182页

作者： Chao Ma Ai-Min Bao Xiao-Xin Yan dick F. swaab Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Human Anatomy Histol-ogy and Embryology Neuroscience Center Joint Laboratory of Anesthesia and Pain School of Basic Medicine Peking Union Medical College Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Institute of Neuroscience NHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Department of Anatomy and Neurobiology Central South University School of Basic Medical Science Department Neuropsychiatric Disorders Netherlands Insti-tute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and Sciences

Human brain banks collect,preserve,and distribute postmortem and biopsied brain samples for histological,pathological,and molecular *** from the western countries,human brain banking in China has remained preliminary over ***,joint efforts during the past few years have substantially promoted this key frontier of neuroscience in *** special topic brings together review and perspective articles on the ethical,administrative,and practical issues of brain *** original studies report molecular and pathological characterizations based on banked human brain samples.

关键词： collect Progress Banking

Quanti?cation of Tyrosine Hydroxylase and Erb B4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin

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Neuroscience Bulletin 2019年第2期35卷 205-215页

作者： Lei Guo Jochem StormmesAND Zheng Fang Qingbin Zhu Rawien Balesar Joop van Heerikhuize Arja Sluiter dick swaab Ai-Min Bao Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Institute of NeuroscienceNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Netherlands Institute for Neuroscience Institute of the Royal Netherlands Academy of Arts and Sciences Department of Neurology Sir Run Run Shaw HospitalZhejiang University School of Medicine

The locus coeruleus(LC) has been studied in major depressive disorder(MDD) and bipolar disorder(BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown *** found significantly increased tyrosine hydroxylase(TH) in the LC of MDD patients—thus validating the method—but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.

关键词： Major depressive disorder Bipolar disorder Tyrosine hydroxylase ErbB4 Locus coeruleus

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

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Neuroscience Bulletin 2019年第2期35卷 244-252页

作者： Xin-Rui Qi Ronald W.H.Verwer Ai-Min Bao Rawien A.Balesar Sabina Luchetti Jiang-Ning Zhou dick F.swaab Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine Department of Neuropsychiatric Disorders Netherlands Institute for NeuroscienceAn Institute of the Royal Netherlands Academy of Arts and Sciences Department of Neurobiology Institute of NeuroscienceNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Key Laboratory of Brain Function and Diseases School of Life SciencesUniversity of Science and Technology of ChinaChinese Academy of Sciences

Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases.A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.

关键词： Alzheimer’s disease Brain bank Brain-derived neurotrophic factor Depression Electrical activity Human brain slice culture Neuropsychiatric disorders Organotypic culture Postmortem human brain tissue Resected human brain tissue

Role of sex hormones on CRH expressing-neurons in the human hypothalamic paraventricular nucleus

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Role of sex hormones on CRH expressing-neurons in the human ...

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： dick F.swaab Netherlands Institute for Neuroscience Meibergdreef 471105 BA Amsterdam ZOThe Netherlands

＜正＞Introduction:The activity of corticotropin-re leasing hormone（CRH） neurons in the hypothalamic paraventricular nucleus（PVN） forms the basis of the activity of the hypothalamo-pituitary-adrenal（HPA）-axis,which is the final common pathway for stress response and for a number of signs and symptoms in specific neurological and psychiatric disorders. A number of studies have pointed to the involvement of sex steroids in the regulation of the stress response and mood *** aimed at determining whether such regulations could be,at least partly,direct effects of sex steroids on the CRH-expressing neurons,via sex hormone ***,the gender difference in age-related number of CRH expressing-neurons and the role of sex hormones on it was also studied. Materials and Methods:Immunocytochemical study:Human hypothalami tissue was obtained from the Netherlands Brain *** monoclonal rat anti-CRH’PFU 83’ antibody and the polyclonal rabbit anti-estrogen receptor（ER）αantibody （MC-20） and polyclonal rabbit anti-androgen receptor（AR） antibody（ARIE） were used for double-labeling of CRH and ERα,and CRH and AR,respectively,in the hypothalamic PVN（virtually no ERβwere found）.CRH and ERαcolocolization was further studied in a depressed-patient-group,which was well-matched for the *** total numbers of CRH neurons in the PVN were also analyzed in 22 control subjects（11 males and 11 females） between the ages of 22 and 89 year, and of 10 subjects with abnormal sex hormone *** assay and co-transfection experiment:The human CRH promoter region was searched and a sequence strongly resembling an androgen responsive element（ARE） was found. Bandshift analysis of this potential ARE was ***,the function of this ARE was investigated by cotransfection of CRH-promoter reporter constructs with AR expression plasmid in SK-N-BE（2）c neuroblastoma ***: Significant correlations between the number of CRH cells and the number of CRH-ERαnuclear

关键词： CRH neurons the HPA axis Sex hormones Mood disorders Aging Sex difference

Brain banking and the matching factors in postmortem study

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Brain banking and the matching factors in postmortem study

中国解剖学会2019年年会

作者： Aimin Bao dick F.swaab Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Institute of NeuroscienceNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Netherlands Institute for Neuroscience an Institute of theRoyal Netherlands Academy of Arts and Sciences

＜正＞Human brain banks collect,preserve,and distribute postmortem brain samples for histological,pathological,and molecular research,with the purpose of especially elucidating human brain *** quality of postmortem study depends strongly on both the clear clinical information of the patient’s disorder and therapies,and a systematic and professional

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Postmortem cerebrospinal fluid levels of hypocretin(Orexin) in major depressive disorder,bipolar disorder patients and controls

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Postmortem cerebrospinal fluid levels of hypocretin(Orexin) ...

2020年浙江省医学会精神病学学术大会浙江省医师协会精...

作者： Jing Lu Haimei Li Rolf Fronczek Manli Huang Aimin Bao dick swaab Yi Xu

Background:Hypocretin(orexin) can markedly affect neurophysiological and behavioral processes in ***,studies measuring hypocretin changes in the human cerebrospinal fluid(CSF) levels of depression patients yield contradictory results so *** addition,postmortem CSF study still lack at this *** study is the first attempt to measure hypocretin level in postmortem CSF ***:Ventricular CSF was obtained from 10 major depressive disorder(MDD) and 5 bipolar disorder(BD)patients and 15 well-matched controls immediately after their *** quantified hypocretin levels in postmortem ventricular CSF using ***:i) Mean CSF hypocretin-1 level in controls was 342.20(282-425) pg/ml,that did not differ to the MDD311.90(191-425) pg/ml or BD 318.20(246-399) pg/ml patients ii) No difference in hypocretin-1 between MDD,BD and control groups either in female(P=0.310) or male(P=0.730) iii) There was no difference of CSF hypocretin-1 in patients with different levels of suicidal ideation(P=0.483).Limitations:Limitations may partly arise from the psychotropic medication used before the death in the study and relatively small size of the ***:To our knowledge,hypocretin levels of postmortem cerebrospinal fluid in in major depressive disorder and bipolar disorder patients were investigated but did not reveal significant differences compared to matched controls.

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Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

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Abnormal retinoid and TrkB signaling in the prefrontal corte...

中国神经科学学会第十届全国学术会议

作者： Jun ZHAO Xin-Rui QI Ji LIU Hui FANG dick F.swaab Jiang-Ning ZHOU Key Laboratory of Brain Function and Diseases School of Life SciencesUniversity of Science and Technology of ChinaChinese Academy of Sciences Netherlands Institute for Neuroscience An Institute of the Royal Netherlands Academy of Arts and Sciences

Objective The prefrontal cortex has structural and functional alterations in mood *** signaling,brain-derived neurotrophic factor（BDNF） and its receptor TrkB are reported to be involved in *** date,there is no information available on the expression pattern of proteins involved in the retinoid signaling in the human PFC nor their alterations in mood ***,even though both retinoid and BDNF-TrkB signaling were known to be associated with depression,it is not clear whether the interactions between the two pathways play a role in the development of depression as they share similarities in neuroplasticity and neurotrophic effects in the central nervous *** In the present study,the mRNA expression levels of major components in the endogenous retinoid signaling,BDNF and TrkB were investigated in the postmortem human PFC and chronic unpredictable mild stressed rats by Quantitative real-time PCR *** relationship between the retinoid and TrkB was identified by immunocytochemistry in postmortem human ACC,further confrmed by chromatin immunoprecipitation（CHIP） assay and Dual luciferase reporter gene assay in cell *** Here we found that mRNA levels of the important elements of retinoid signaling were significantly reduced in the postmortem dorsolateral prefrontal cortex/anterior cingulate cortex from elderly non-suicidal depressed *** mRNA levels of BDNF and TrkB isoforms were also *** alterations were observed in a rat model for *** with neurons immunopositive for both retinoic acid receptor-α（RARα） and TrkB,a positive correlation between mRNA levels of the two receptors was found in the anterior cingulate cortex of control subjects but not of depressed patients,suggesting the interaction between them was *** vitro studies showed that RARα was able to bind to and transactivate the TrkB promoter via a putative retinoic acid response element within the TrkB promoter

关键词： anterior cingulate cortex brain-derived neurotrophic factor depression dorsolateral prefrontal cortex retinoic acid receptor-α

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自杀和生命的意义——来自脑科学研究的解读

浙江大学学报（人文社会科学版） 2015年第4期45卷 109-120页

作者：包爱民迪克.斯瓦伯浙江大学医学院浙江杭州310058 荷兰皇家艺术与科学院神经科学研究所

生命本身是一个随机事件,并不具有高尚的意义。进化的结果使人类可通过工作、家庭和人际关系等给予自己的生命以意义感。当我们的生活方式使脑内奖赏系统获得刺激,就会带来生命具有意义的感受,这种感受给人带来更好的生存机会。生存的... 详细信息

生命本身是一个随机事件,并不具有高尚的意义。进化的结果使人类可通过工作、家庭和人际关系等给予自己的生命以意义感。当我们的生活方式使脑内奖赏系统获得刺激,就会带来生命具有意义的感受,这种感受给人带来更好的生存机会。生存的欲望是一切生物体最具特征的属性,一些精神疾病患者缺乏这种欲望。自杀主要发生于精神疾病患者,它并非是基于自由意志的行为。抗精神病治疗和适当的社会交往可以预防自杀。由于不同个体有着不同的大脑,人们的生活方式就应该去适应各自大脑的特征。只要人们的生活方式不对他人造成过多的伤害,政府就应该允许和保护人们自由地按照各自的方式生活。

关键词：神经科学自杀大脑生命的意义自由意志