Procurement and Characterization of Postmortem Brain Tissue

死后脑组织的获取和表征

基本信息

批准号：
10922460
负责人：
Stefano Marenco
金额：
$ 471.1万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10922460
关键词：
17q21 2019-nCoV Acetylation Alcohol dependence Alzheimer&apos s Disease Amygdaloid structure Anterior Anxiety Disorders Applications Grants Atlases Attention Deficit Disorder Attention deficit hyperactivity disorder Audiotape Authorization documentation Autopsy Behavior Biological Assay Bipolar Disorder Blood brain barrier dysfunction Blood specimen Brain Brain Mapping Brain region COVID-19 Cadaver Cell Communication Cell Nucleus Cells Cessation of life ChIP-seq Chromatin Fiber Classification Claustral structure Clinical Code Collection Communities Consent DNA DNA Methylation Data Development Diabetes Mellitus Diagnosis Diagnostic Diffusion Dorsal Dura Mater Electronic Mail Electronics Endogenous Retroviruses Equipment and supply inventories Equity Evaluation Exposure to Family Fentanyl Fibroblasts Formalin Frozen Sections Genetic Genetic Transcription Genetic study Genotype Goals Habenula Hair Haplotypes Hippocampus Hormonal Human Human Genome Human Resources Hypothalamic structure Immunization Individual Institution International Classification of Diseases Interview Intramural Research Program Iron JC Virus Label Letters Magnetic Resonance Imaging Major Depressive Disorder Major Mental Illness Medial Medical Medical Examiners Medical Records Menopausal Status Mental Depression Mental Health Mental disorders Methylation Mission Molecular Multiple Sclerosis Muscle Mutation National Institute of Mental Health Nerve Degeneration Neuroanatomy Neuropathogenesis Obsessive-Compulsive Disorder Ovary Parkinsonian Disorders Patients Polymers Post-Traumatic Stress Disorders Prefrontal Cortex Preparation Prevalence Prevention strategy Process Progressive Multifocal Leukoencephalopathy Psychiatric Diagnosis Psychotic Disorders Puberty Pulvinar structure RNA Recording of previous events Regulation Reporting Research Research Personnel Research Support Resources Role SARS-CoV-2 exposure SARS-CoV-2 infection Sampling Schizoaffective Disorders Schizophrenia Serology test Services Sleep Slice Slide Specimen Structure of choroid plexus Substance Use Disorder Substance abuse problem Substantia nigra structure Suicide Superior temporal gyrus Surface Swab Synapses Testing Thalamic structure Thick Time Tissue Sample Tissues Toxicology Tubulin United States National Institutes of Health Validation Variant Virginia Virus Virus Diseases Woman amyloid formation autism spectrum disorder biological sex brain dysfunction brain tissue cDNA Library cell type cingulate cortex data archive database of Genotypes and Phenotypes density effective therapy energy balance frontal lobe genome sequencing genome-wide genomic data metabolome multiple omics nervous system disorder neuroinflammation neuropathology novel therapeutics pathogen polymerization protein aggregation public database reproductive sample collection sex single nucleus RNA-sequencing spectrograph suicidal behavior transcriptome transcriptome sequencing transcriptomic profiling transcriptomics web site whole genome

项目摘要

Currently, the Human Brain Collection Core (HBCC) has 1307 brains available for distribution, with the following diagnoses (numbers of subjects listed in parentheses): attention deficit disorder (24); anxiety disorders (27); autism spectrum disorders (5); Bipolar disorder (156), Non-psychiatric controls (339), severe psychotic disorders (including schizophrenia and schizoaffective disorder: 193), substance use disorders (129), Major depressive disorder (281), post-traumatic stress disorder (15), obsessive compulsive disorder (15), Other psychiatric diagnoses (68), Undetermined (32), COVID-19 infections at time of death (6), progressive multifocal leukoencephalopathy (2), various neurological disorders (15). In 19 cases, the diagnosis is still pending. From Oct 1, 2022, until July 18, 2023 we collected 28 brains through Northern and Central Virginia OCMEs. Additional resources include: -cDNA libraries constructed from dorsolateral prefrontal cortex (DLPFC), hippocampus, anterior cingulate cortex (ACC) and subgenual anterior cingulate cortex (sgACC), and dura from hundreds of subjects with psychiatric disorders and controls -microarray expression and genotyping data (publicly available at the NIMH data archive (NDA: https://nda.nih.gov/edit_collection.html?id=3151) from DLPFC, hippocampus and dura -frozen sections (14 um thick) mounted on slides (DLPFC from 16 patients with schizophrenia and 34 controls remaining), -formalin-fixed coronal slices (approximately 15 mm thick) of a single hemisphere from 15 controls, 10 patients with schizophrenia, 5 with major depression, 4 with bipolar disorder. -Fibroblasts derived from postmortem dura: 48 individuals. -Whole genome sequencing, RNA sequencing, and Chip-sequencing (acetylation and methylation marks) data for DLPFC of 400 subjects (publicly available at NDA: https://nda.nih.gov/edit_collection.html?id=3151), on the CommonMind Consortium portal and on the PsychEncode resource page: http://resource.psychencode.org/) -RNA sequencing data from 200 individuals from the subgenual ACC, 219 from the Superior Temporal Gyrus and 311 from the dorsal anterior cingulate are also available on NDA (https://nda.nih.gov/edit_collection.html?id=3151). DNA methylation data from cases with schizophrenia (dorso-lateral prefrontal cortex N=216), bipolar disorder (hippocampus, N=64) and neurotypical controls have been added to the collection in the last year, together with single nucleus RNA-sequencing data of two brain regions (subgenual anterior cingulate and dorso-lateral prefrontal cortex) for eight neurotypical cases . We share information with Neurobiobank (NBB). Our inventory of cases is accessible through the Neurobiobank website (https://neurobiobank.nih.gov/). We obtain detailed quantitative electronic toxicological data on hundreds of our specimens and share them with NBB. We use international classification of diseases (ICD10) codes for diagnostic classification. Since Oct 1 2022, we have responded to 41 requests, including 18 from the Intramural Research Program (tissue, data or services), 6 letters of support for grant applications, and 17 external requests for tissue or data. We have distributed 1170 tissue samples this 9 month period, including 974 to NIH and 196 to other institutions. We have also shared large genomic datasets. We test all donors for COVID-19 with a nasopharingeal swab of the cadaver and serology testing. We have identified six cases positive for active SARS-CoV2 infection and 51 cases with evidence of prior exposure to SARS-CoV2, and 18 cases with evidence of immunization but no prior exposure to the virus. All donors were not known to be symptomatic at the time of death. Our list of active tissue and data requests includes: 1. Characterizing long-read RNA transcriptomes from post-mortem brains of patients with schizophrenia 2. Comprehensive characterization of 1,198 deep whole genomes from the Human Brain Collection Core for genetic and functional studies of suicidal behavior 3. Muscle-brain crosstalk in anxiety disorders: A new avenue for developing effective treatments 4. Postmortem identification of the reproductive/menopausal status in women and other individuals with ovaries 5. Cell type specific single chromatin fiber profiling on a genome-wide scale in frontal cortex of bipolar, schizophrenia and control subjects 6. Multi-Omics of 17q21.31 Haplotypes in brain tissues 7. Characterizing human blood-brain barrier dysfunction during alcohol dependence 8. Investigating the role of hormonal surges during puberty on cell-specific gene transcription and the potential influence on sex-skewed prevalences in major depression 9. Synaptic density in Schizophrenia 10. Fentanyl-induced neurodegeneration in the CA3 region of the hippocampus 11. Single-Cell Transcriptomic Analysis of the PFC and ACC in ADHD patients 12. Effect of diabetes on Biondi body amyloid formation in the choroid plexus 13. Association of SARS-CoV-2 infection and Alzheimers-like neuropathology 14. The regulation of m6A on hypothalamus development and function of energy balance 15. Single-nucleus transcriptomes in the habenula in Major Depressive Disorder 16. Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia 17. Spatial transcriptomics (Visium) pilot on the amygdala 18. Multi-omics of the ADHD brain 19. Unraveling the role of GBA1-mutations in parkinsonism 20. Single Nuclei Atlas of the Human Substantia Nigra 21. Single Nuclei Atlas of the Human Prefrontal Cortex 22. Cell-type specific distribution of ALDH2 in human choroid plexus 23. Cell - cell interaction in Multiple sclerosis based on single nucleus RNAseq (snRNAseq) 24. A role for the medial pulvinar in schizophrenia 25. Optimization of spatial transcriptomics profiling of human mediodorsal thalamus 26. Biological sex effects on the human brain transcriptome and metabolome 27. Exploring host pathogen interactions in JC virus infection and PML progression using Visiums FFPE spatial transcriptomics assay. 28. Mapping brain iron variation across cortical surface and subcortical regions with T2-based ultra-high-field 7T magnetic resonance imaging 29. Tubulin polymerization promoting protein (TPPP) aggregation in schizophrenia 30. The relationship between sleep and claustrum. 31. HERV-K Neuropathogenesis in ALS

目前，人脑收集核心（HBCC）有1307个大脑可分发，并进行以下诊断（括号中列出的受试者数量）：注意力不足障碍（24）；焦虑症（27）；自闭症谱系障碍（5）；躁郁症（156），非精神病患者（339），严重的精神病（包括精神分裂症和精神分裂症障碍：193），药物使用障碍（129），严重的抑郁症（281），术后压力障碍（15），经济学后压力障碍（15），强迫性疾病（15）（15），其他精神疾病（68）（32），32（32）死亡时的感染（6），进行性多灶性白细胞症（2），各种神经系统疾病（15）。在19例病例中，诊断仍在等待中。从2022年10月1日到2023年7月18日，我们通过北部和中部弗吉尼亚州OCME收集了28个大脑。其他资源包括： -CDNA库由背外侧前额叶皮层（DLPFC），海马，前扣带回皮层（ACC）和亚果位前扣带回皮层（SGACC）以及具有精神疾病和对照的数百个主体的硬脑膜 -Microarray表达和基因分型数据（在NIMH数据档案中公开获得（NDA：https：//nda.nih.gov/edit_collection.html?id=3151），来自DLPFC，Hippocampus和Dura - 安装在载玻片上（16例精神分裂症患者的DLPFC和34例对照的dlpfc）的frozen切片（14 um厚）， - 15个对照组的一个半球，10例精神分裂症患者，5例严重抑郁症，4例双相情感障碍。 - 造后硬脑膜衍生的纤维细胞：48个个体。 - 全基因组测序，RNA测序以及400名受试者DLPFC的DLPFC数据（乙酰化和甲基化标记）数据（可在NDA上公开获取：https：//nda.nih.gov/edit_collection.html?ID=3151） http://resource.psychencode.org/） -RNA测序来自来自亚属ACC的200个个体的数据，来自上颞回的219个，在NDA（https://nda.nih.gov/edit_collection.html?id=3151）上也可获得。去年，已将精神分裂症病例（多索外侧前皮质皮质n = 216），双相情感障碍（海马，n = 64）和神经型对照组的DNA甲基化数据添加到了该集合中神经型病例。我们与Neurobiobank（NBB）共享信息。我们的案件清单可通过Neurobiobank网站（https://neurobiobank.nih.gov/）访问。我们在数百个标本上获得了详细的定量电子毒理数据，并与NBB共享。我们使用国际疾病分类（ICD10）代码进行诊断分类。自2022年10月1日以来，我们已经回应了41条请求，其中包括壁内研究计划（组织，数据或服务）的18个请求，6份授予申请的6封支持信和17个有关组织或数据的外部请求。我们在这个9个月期间分配了1170个组织样品，其中974个向NIH分配给其他机构。我们还共享了大型基因组数据集。我们用尸体和血清学测试的鼻签进行了所有捐赠者的供体。我们已经确定了六例活跃的SARS-COV2感染和51例阳性病例，并证明了先前暴露于SARS-COV2的证据，以及18例具有免疫证据的病例，但没有事先暴露于该病毒。所有捐助者在死亡时并不是有症状的。我们的活动组织和数据请求列表包括： 1。表征精神分裂症患者验尸大脑的长读RNA转录组 2。从人脑收集核心的1,198个深基因组的全面表征，用于自杀行为的遗传和功能研究 3。焦虑症中的肌肉脑串扰：开发有效治疗的新途径 4。验尸识别妇女和其他卵巢的生殖/绝经状况 5。细胞类型特异性单染色质纤维分析在双极，精神分裂症和对照对象的额叶皮层中的全基因组尺度上 6。脑组织中的17q21.31单倍型的多词 7。表征酒精依赖期间人类血脑屏障功能障碍 8。研究青春期中激素激增对细胞特异性基因转录的作用，以及对重度抑郁症的性扭转率的潜在影响 9。精神分裂症的突触密度 10。芬太尼诱导的海马CA3区域的神经退行性 11。多动症患者的PFC和ACC的单细胞转录组分析 12。糖尿病对脉络丛中Biondi体淀粉样蛋白形成的影响 13。SARS-COV-2感染与阿尔茨海默氏症类神经病理学的关联 14. M6A对下丘脑发展和能量平衡功能的调节 15。主要抑郁症的Habenula中的单核转录组 16。精神分裂症中神经炎症的扩散基频谱成像的验证 17。杏仁核上的空间转录组学（visium）飞行员 18。多动症大脑的多词 19。阐明GBA1突变在帕金森氏症中的作用 20。人本底的单核地图集 21。人前额叶皮层的单核地图集 22。人脉络丛中AldH2的细胞类型特异性分布 23。基于单核RNASEQ（SNRNASEQ）的多发性硬化症中的细胞 - 细胞相互作用 24。在精神分裂症中内侧肺泡的作用 25.人类中腹丘脑的空间转录组学分析的优化 26。生物学对人脑转录组和代谢组的影响 27。使用vfpe空间转录组学测定法探索JC病毒感染和PML进展中的宿主病原体相互作用。 28。用基于T2的超高场7T磁共振成像的皮质表面和皮层下区域的脑铁变异 29。精神分裂症中促进蛋白质（TPPP）聚集的微管蛋白聚合 30。睡眠和claustrum之间的关系。 31。ALS中的HERV-K神经病发生

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cellular Diversity in Human Subgenual Anterior Cingulate and Dorsolateral Prefrontal Cortex by Single-Nucleus RNA-Sequencing.

通过单核 RNA 测序研究人类膝下前扣带皮层和背外侧前额叶皮层的细胞多样性。

DOI：
10.1523/jneurosci.0830-22.2023
发表时间：
2023
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Kim,Billy;Kim,Dowon;Schulmann,Anton;Patel,Yash;Caban-Rivera,Carolina;Kim,Paul;Jambhale,Ananya;Johnson,KoryR;Feng,Ningping;Xu,Qing;Kang,SunJung;Mandal,Ajeet;Kelly,Michael;Akula,Nirmala;McMahon,FrancisJ;Lipska,Barbara;Mare
通讯作者：
Mare

Genetic variation in FGF20 modulates hippocampal biology.

DOI：
10.1523/jneurosci.5773-09.2010
发表时间：
2010-04-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Lemaitre H;Mattay VS;Sambataro F;Verchinski B;Straub RE;Callicott JH;Kittappa R;Hyde TM;Lipska BK;Kleinman JE;McKay R;Weinberger DR
通讯作者：
Weinberger DR

Metabotropic glutamate receptor 2 and 3 gene expression in the human prefrontal cortex and mesencephalon in schizophrenia.

DOI：
10.1080/00207450802330702
发表时间：
2008-11
期刊：
The International journal of neuroscience
影响因子：
0
作者：
Ghose S;Crook JM;Bartus CL;Sherman TG;Herman MM;Hyde TM;Kleinman JE;Akil M
通讯作者：
Akil M

Expression of kinase interacting with stathmin (KIS, UHMK1) in human brain and lymphoblasts: Effects of schizophrenia and genotype.

DOI：
10.1016/j.brainres.2009.08.090
发表时间：
2009-12-08
期刊：
BRAIN RESEARCH
影响因子：
2.9
作者：
Bristow, Greg C.;Lane, Tracy A.;Walker, Mary;Chen, Li;Sei, Yoshi;Hyde, Thomas M.;Kleinman, Joel E.;Harrison, Paul J.;Eastwood, Sharon L.
通讯作者：
Eastwood, Sharon L.

Temporal dynamics and genetic control of transcription in the human prefrontal cortex.

DOI：
10.1038/nature10524
发表时间：
2011-10-26
期刊：
NATURE
影响因子：
64.8
作者：
Colantuoni, Carlo;Lipska, Barbara K.;Ye, Tianzhang;Hyde, Thomas M.;Tao, Ran;Leek, Jeffrey T.;Colantuoni, Elizabeth A.;Elkahloun, Abdel G.;Herman, Mary M.;Weinberger, Daniel R.;Kleinman, Joel E.
通讯作者：
Kleinman, Joel E.