A National Resource for Postmortem Brain Research

描述（由申请人提供）：这是哈佛脑组织资源中心的竞争性更新申请，该中心是一个国家资源，用于向神经科学界获取，处理，存储和分发高质量的死后（PM）大脑。该设施收集正常对照（CON）以及患有各种运动障碍（亨廷顿舞蹈病和帕金森病）、痴呆（阿尔茨海默病、额颞叶痴呆）和主要精神病（精神分裂症和双相情感障碍）的个体的大脑。HBTRC将组织标本分发给全美的神经解剖学家、神经病理学家、神经药理学家、神经化学家和分子生物学家。在过去的5年中，该组织发表了170多篇科学论文。在目前的供资期间，卫生保健和资源中心进行了重大改组，从而提高了其业务的总体质量和效率。这次重组的一个重要成果是新鲜和冷冻病例数量的增加以及尸检间隔（PMI）的显著减少。由于这一努力，丰富的，高质量的组织现在可用于广泛的最先进的研究应用。在目前的资助期内，HBTRC收到的con数量增加了一倍以上，HBTRC现在能够为研究人员提供与年龄、PMI、性别和半球相匹配的con和患病大脑。对于主要精神病患者来说，获取死后大脑实际上是具有挑战性的，精神分裂症和双相情感障碍病例的数量也有所增加。由于这些主要来自社区转诊，因此收容、缺乏营养和滥用药物的潜在混淆影响相对低于法医案件。为了促进捐赠过程，HBTRC建立了一个网站，其中包括：a)潜在捐赠者及其家属的知情同意书，b)参与脑切除的病理学家或研究人员处理大脑的说明，以及c)为研究人员寻找组织的申请表。HBTRC还开发了一个用户互动数据库，以便从“库”接收组织的调查人员可以获得其病例的人口统计数据、神经病理学报告、大体解剖图像和组织学切片。在NIH的补充资助下，HBTRC现在正在使用标准Affymetrix微阵列系统获得基因表达谱和SNP分析，这些信息一经获得将立即放入我们的公共领域国家数据库。所有接受HBTRC组织的研究人员也将被鼓励将他们的发现“存入”数据库，以便神经科学界可以进行复杂的关系分析。在下一个筹资期内，这些新举措将加强“脑库”作为一项重要国家资源的功能。

DESCRIPTION (provided by applicant): This is a competitive renewal application for the Harvard Brain Tissue Resource Center, a national resource for the acquisition, processing, storage and distribution of high quality postmortem (PM) brain to the neuroscience community. This facility collects brains from normal controls (CON), as well as individuals with a variety of movement disorders (Huntington's chorea and Parkinson's disease), dementias (Alzheimer's disease, frontotemporal dementias) and major psychoses (schizophrenia and bipolar disorders). The HBTRC distributes tissue specimens to neuroanatomists, neuropathologists, neuropharmacologists, neurochemists and molecular biologists throughout the U.S. Over the past 5 years, this tissue has contributed to more than 170 scientific publications. During the current funding period, the HBTRC has undergone a major restructuring that has resulted in an increase in the overall quality and efficiency of its operation. An important outcome of this re-organization has been an increase in the number of fresh, frozen cases and a marked decrease in the postmortem interval (PMI). As a result of this effort, abundant, high quality tissue is now available for a broad array of state-of-the-art research applications. The number of CONs received by the HBTRC has more than doubled during the current funding period and the HBTRC is now able to provide investigators with sets of CONs and diseased brains matched for age, PMI, gender and hemisphere. For the major psychoses, where the acquisition of postmortem brains is actually challenging, the number of schizophrenic and bipolar cases has also increased. Since these are largely from community-based referrals, the potential confounding effects of institutionalization, inanition and substance abuse are relatively lower than in medical examiner cases. To facilitate the donation process, the HBTRC has established a website with a) Informed Consent forms for potential donors and their families, b) instructions for handling brains by pathologists or dieners involved in brain removal, and c) application forms for investigators seeking tissue for their research. The HBTRC has also developed a User-Interactive Database, so that investigators who receive tissue from the "bank" can obtain demographics, neuropathology reports and images of gross dissections and histological slides for their cases. With supplemental funding from NIH, the HBTRC is now obtaining gene expression profiling and SNP analyses using the standard Affymetrix microarray system and this information will be immediately placed in our public domain National Databank as it is obtained. All investigators receiving tissue from the HBTRC will also be encouraged to "deposit" their findings in the Databank so that they will be available to the neuroscience community for complex relational analyses. Over the next funding period, these new initiatives will enhance the functioning of the "brain bank" in its role as a vital national resource.