EFFECTS OF TESTOSTERONE ON ADULT NEUROGENESIS IN THE DENTATE GYRUS

睾酮对齿状回成人神经发生的影响

• 批准号: 7959881
• 负责人: Mark D. Spritzer
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959881
• 关键词: Adult; Brain; Bromodeoxyuridine; Cell Survival; Cells; Computer Retrieval of Information on Scientific Projects Database; Funding; Genetic; Grant; Hippocampus (Brain); Institution; Label; Learning; Memory; Neurons; Oils; Performance; Proliferating; Radial; Rattus; Research; Research Personnel; Resources; Running; Short-Term Memory; Source; Staining method; Stains; Testing; Testosterone; Testosterone Propionate; United States National Institutes of Health; Upper arm; Vermont; Work; adult neurogenesis; dentate gyrus; improved; male; neurogenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous research indicates that testosterone enhances the survival of newly proliferated neurons in the adult hippocampus, and increased survival of hippocampal neurons may correlate with improved spatial memory. Therefore, adult neurogenesis may be the mechanism by which testosterone improves spatial working memory. We examined both performance on a working-reference memory version of the 8-arm radial maze (RAM) and 30-day hippocampal cell survival using castrated adult male rats. Subjects were injected with BrdU (200 mg/kg) to assess the survival of newly proliferated cells within the hippocampus. Beginning the following day, rats were run once daily for 29 days on the RAM. The number of both working memory errors (WME) and reference memory errors (RME) was scored. Each day prior to maze testing, rats were injected with either 0.5 mg of testosterone propionate (n = 10) or 0.1ml of oil vehicle (n = 10). BrdU-labeled cells were stained and scored on brain sections. Testosterone-injected subjects performed significantly fewer WMEs than did controls during the first ten days of testing. In contrast, testosterone had no significant effect on RMEs. This indicates that testosterone improves working memory but not reference memory. Surprisingly, testosterone had no effect on cell survival. This may have been because learning on the maze elevated neurogenesis levels in the control subjects. These results suggest that enhanced hippocampal cell survival may not be the mechanism by which testosterone improves spatial memory.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 先前的研究表明，睾酮可提高成年海马体中新增殖的神经元的存活率，而海马体神经元存活率的提高可能与空间记忆的改善相关。因此，成人神经发生可能是睾酮改善空间工作记忆的机制。我们使用阉割的成年雄性大鼠检查了 8 臂径向迷宫 (RAM) 工作参考记忆版本的表现和 30 天海马细胞存活率。受试者注射 BrdU（200 毫克/千克）以评估海马内新增殖细胞的存活率。从第二天开始，大鼠每天在 RAM 上跑步一次，持续 29 天。对工作记忆错误（WME）和参考记忆错误（RME）的数量进行评分。每天在迷宫测试之前，给大鼠注射 0.5 毫克丙酸睾酮 (n = 10) 或 0.1 毫升油载体 (n = 10)。 BrdU 标记的细胞在脑切片上进行染色和评分。在测试的前十天内，注射睾酮的受试者的 WME 明显少于对照组。相比之下，睾酮对 RME 没有显着影响。这表明睾酮可以改善工作记忆，但不能改善参考记忆。令人惊讶的是，睾酮对细胞存活没有影响。这可能是因为在迷宫中学习提高了对照组受试者的神经发生水平。这些结果表明，海马细胞存活率的提高可能不是睾酮改善空间记忆的机制。