Relationship between neuroactive molecules and cognitive functions in the aged monkey prefrontal cortex

本项目旨在阐明老年猴前额叶皮层神经活性分子与认知功能之间的关系。研究了老年猕猴前额叶皮层和海马结构中脑源性神经营养因子（BDNF）免疫反应结构的变化。在成年期（5岁、10岁和12岁），在前额皮质第II、III、V和VI层锥体神经元中观察到bdnf免疫反应性。在海马形成中，BDNF免疫反应发生在齿状回神经元、CA1、CA2、CA3亚区的锥体神经元和枕下。在老年猴子（26岁、30岁和32岁）中，前额皮质和海马形成的神经元细胞体和树突中的bdnf免疫反应性强度显著下降（Brain Res. 918: 191- 196,2001）。此外，我们研究了年龄（25岁、27岁和28岁）和年轻（6岁和10岁）的猴子，使用多重位置反转任务来研究认知功能随年龄增长而下降的情况。在这项任务中，年老的猴子表现得比年轻的猴子差。根据我们的反应分析，老年猴子在逆向学习中的表现不佳主要不是由于错误反应的重复，而是由于对刺激和奖励之间关系的理解受损。我们现在正在研究这些老年和年轻猴子前额皮质bdnf免疫反应性的变化。我们还发现，TrkB亚型与BDNF二聚化的转变发生在猴子前额叶皮层的衰老过程中(J. Neurosci。Res. 65: 463-469, 2001)。

The purpose of this project is to clarify the relationship between neuroactive molecules and cognitive functions in the aged monkey prefrontal cortex. We investigated the changes of brain-derived neurotrophic factor (BDNF)-immunoreactive structures in the prefrontal cortex and the hippocampal formation of aged macaques (Macaca fuscata fuscatd). At the adult stages (5, 10 and 12 years), BDNF-immunoreactivity was observed in the pyramidal neurons in layers II, III, V and VI of the prefrontal cortex. In the hippocampal formation, BDNF immunoreactivity occurred in the neurons of the dentate gyrus, the pyramidal neurons in the CA1, CA2, CA3 subfields and the subiculum. In aged monkeys (26, 30 and 32 years), the intensity of the BDNF-immunoreactivity declined significantly in cell bodies and dendrites of neurons in the prefrontal cortex and the hippocampal formation (Brain Res. 918 : 191-196, 2001). In addition, we examined aged (25, 27 and 28 years) and young monkeys (6 and 10 years) using a multiple position reversal task to investigate declines in cognitive functions with aging. Aged monkeys showed a poorer performance than the young monkeys in this task. According to our response analysis, the poor performance of aged monkeys in the reversal learning was not caused mainly by repetition of error responses, but rather by the impairment of an understanding of the association between stimulus and reward. We are now investigating changes in BDNF-immunoreactivity of the prefrontal cortex of these aged and young monkeys. We also found that transitions in the dimerization of TrkB subtypes with BDNF occurred during aging of the monkey prefrontal cortex (J. Neurosci. Res. 65 : 463-469, 2001).