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续签申请，哈佛脑组织资源中心是一家全国性的资源，旨在获取、处理、存储高质量的尸检(PM)脑，并将其分发给神经科学界。该机构收集正常人(CON)以及患有各种运动障碍(亨廷顿舞蹈症和帕金森病)、痴呆症(阿尔茨海默病、额颞痴呆)和严重精神病(精神分裂症和双相情感障碍)的人的大脑。HBTRC将组织标本分发给美国各地的神经解剖学家、神经病理学家、神经药剂学家、神经化学家和分子生物学家。在过去的5年里，该组织为170多篇科学出版物撰稿。在本供资期间，HBTRC进行了重大重组，从而提高了其运作的整体质量和效率。这一重组的一个重要结果是，新鲜、冷冻病例的数量增加，死亡间隔时间明显减少。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。在当前的资助期间，HBTRC收到的CONS数量增加了一倍多，HBTRC现在能够向调查人员提供一组与年龄、PMI、性别和大脑半球匹配的CONS和患病大脑。对于主要的精神病患者来说，死后大脑的获取实际上是一种挑战，精神分裂症和双相情感障碍的病例数量也有所增加。由于这些主要是基于社区的转介，制度化、空虚和药物滥用的潜在混杂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，上面有a)潜在捐赠者及其家人的知情同意书，b)参与脑切除的病理学家或Dieners处理大脑的说明，以及c)调查人员为他们的研究寻找组织的申请表。HBTRC还开发了一个用户交互数据库，以便从“银行”接收组织的调查人员可以获得他们的病例的人口统计数据、神经病理报告以及大体解剖和组织切片的图像。在NIH的补充资助下，HBTRC现在正在使用标准的Affymetrix微阵列系统获得基因表达谱和SNP分析，这些信息将在获得时立即放入我们的公共领域国家数据库中。所有从HBTRC收到组织的研究人员也将被鼓励将他们的发现“存放”在数据库中，以便神经科学界可以用于复杂的关系分析。在下一个资金阶段，这些新举措将加强“脑库”作为国家重要资源的作用。

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.