TESTOSTERONE, HIPPOCAMPAL NEUROGENESIS, AND SPATIAL MEMORY IN ADULT MALE RATS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 先前的研究表明，睾酮可以提高成年海马区新增殖神经元的存活率，而海马神经元存活率的提高可能与改善空间记忆有关。因此，成人神经发生可能是睾酮改善空间工作记忆的机制。我们在8臂径向迷宫(RAM)的工作参考记忆版本上测试了性能，并使用去势成年雄性大鼠检测了30天的海马细胞存活。受试者注射BrdU(200 mg/kg)，以评估海马区新增殖细胞的存活情况。从第二天开始，大鼠在随机存取存储器上每天运行一次，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。迷宫测试前每天给大鼠注射丙酸睾丸酮0.5 mg(n=10)或油剂0.1ml(n=10)。对BrdU标记细胞进行染色，并在脑切片上进行评分。在测试的前十天，注射睾丸激素的受试者的WME明显少于对照组。相比之下，睾丸激素对RME没有显著影响。这表明，睾丸激素改善了工作记忆，但不能改善参考记忆。令人惊讶的是，睾丸激素对细胞存活没有影响。这可能是因为在迷宫中的学习提高了对照组受试者的神经发生水平。这些结果表明，提高海马细胞存活率可能不是睾酮改善空间记忆的机制。

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.