BARDGETT POST-DOC/TECHNICIAN SUPPORT

BARDGETT 博士后/技术员支持

• 批准号: 8360102
• 负责人: MARK Edward BARDGETT
• 金额: $ 6.39万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360102
• 关键词: Adult; Award; Behavioral; Biomedical Research; Cognitive; Data; Dorsal; Funding; Goals; Grant; Hippocampus (Brain); Histamine H3 Receptors; Infusion procedures; Injury; Memory; Memory impairment; Modeling; Mollies; Motor Activity; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; National Center for Research Resources; Neonatal; Paper; Pharmaceutical Preparations; Postdoctoral Fellow; Prefrontal Cortex; Principal Investigator; Publishing; Rattus; Request for Applications; Research; Research Infrastructure; Resources; Short-Term Memory; Source; United States National Institutes of Health; cost; improved; prepulse inhibition

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the proposed research is to develop and use models of modest excitotoxic hippocampal injury to assess the cognitive enhancing ability of specific candidate compounds. Our preliminary data demonstrate that excitotoxic injury to the dorsal hippocampus produces enduring deficits in spatial working memory. We have also shown in preliminary studies that antagonists at histamine H3 receptors alleviate injury-induced deficits in spatial working memory. The specific aims of our currently-funded R15 research have been to answer the following questions: 1) Can H3 antagonists alleviate spatial working memory deficits in rats with adult-onset hippocampal injury, 2) Can direct infusion of H3 antagonists into the prefrontal cortex improve memory in rats with adult-onset hippocampal injury, & 3) Can H3 antagonists alleviate changes in spatial working memory, prepulse inhibition, and locomotor activity in rats with neonatal-onset hippocampal injury? For this application, we requested INBRE supplemental support for a research associate who can advance the aims of our R15 research and supervise undergraduate research. Between May 2009 and the present, we have assessed the effects of H3 antagonists on spatial memory deficits and other behavioral anomalies produced by drugs that block NMDA receptors. These studies, mainly performed by Molly Griffith, our research associate, and several undergraduates in the lab, have shown that H3 antagonists exacerbate the effects of NMDA antagonists on locomotor activity, but also alleviate the spatial memory deficits produced by such drugs. We submitted an R15 to continue these studies in June 2009 and it received a priority score of 37. We will revise and resubmit this application in February 2010. Having INBRE support for our research associate has greatly facilitated the pace of our R15 research and resulted in two published papers, support for award-winning undergraduate research, and an R15 renewal application that received a favorable (although unfundable) score.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 拟议研究的目标是开发和使用中度兴奋毒性海马损伤模型来评估特定候选化合物的认知增强能力。我们的初步数据表明，背侧海马的兴奋性毒性损伤会导致空间工作记忆的持久缺陷。我们还在初步研究中表明，组胺 H3 受体拮抗剂可以减轻损伤引起的空间工作记忆缺陷。我们目前资助的 R15 研究的具体目标是回答以下问题：1) H3 拮抗剂能否缓解成年海马损伤大鼠的空间工作记忆缺陷，2) 直接将 H3 拮抗剂注入前额叶皮层可以改善成年海马损伤大鼠的记忆，3) H3 拮抗剂能否减轻新生儿海马损伤大鼠的空间工作记忆、前脉冲抑制和运动活动的变化海马损伤？对于此申请，我们请求 INBRE 为一名研究员提供补充支持，该研究员可以推进我们的 R15 研究目标并监督本科生研究。 2009 年 5 月至今，我们评估了 H3 拮抗剂对空间记忆缺陷和其他由阻断 NMDA 受体的药物引起的行为异常的影响。这些研究主要由我们的研究员 Molly Griffith 和实验室的几名本科生进行，研究表明 H3 拮抗剂会加剧 NMDA 拮抗剂对运动活动的影响，但也会减轻此类药物产生的空间记忆缺陷。我们于 2009 年 6 月提交了 R15 来继续这些研究，并获得了 37 分的优先级分数。我们将在 2010 年 2 月修改并重新提交该申请。INBRE 对我们研究助理的支持极大地促进了我们 R15 研究的步伐，并导致两篇发表的论文，对获奖本科生研究的支持，以及获得有利（尽管无法资助）分数的 R15 续签申请。