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

老年猴前额皮质神经活性分子与认知功能的关系

基本信息

批准号：
12680772
负责人：
HAYASHI Motoharu
金额：
$ 2.37万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680772/
关键词：
macaque Prefrontal cortex neuroactive molecule aging Cognitive function BDNF TrkB 霊長類脳由来神経栄養因子海馬

项目摘要

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).

该项目的目的是阐明老年猴前额皮质神经活性分子与认知功能之间的关系。我们研究了老年猕猴（Macaca fuscata fuscatd）前额皮质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。在成年阶段（5、10和12岁），在前额叶皮层II、III、V和VI层的锥体神经元中观察到BDNF免疫反应性。在海马结构中，BDNF 免疫反应性发生在齿状回神经元、CA1、CA2、CA3 亚区和下托的锥体神经元中。在老年猴子(26、30和32岁)中，前额皮质和海马结构中神经元的细胞体和树突中的BDNF免疫反应性强度显着下降(Brain Res.918：191-196，2001)。此外，我们还使用多位置反转任务对老年人（25 岁、27 岁和 28 岁）和年轻猴子（6 岁和 10 岁）进行了检查，以调查认知功能随衰老而下降的情况。在这项任务中，老年猴子的表现比年轻猴子差。根据我们的反应分析，老年猴子在逆向学习中表现不佳的主要原因并不是重复错误反应，而是由于对刺激和奖励之间的关联的理解受损。我们现在正在研究这些年老和年轻猴子的前额皮质 BDNF 免疫反应性的变化。我们还发现，TrkB 亚型与 BDNF 的二聚化转变发生在猴子前额皮质的衰老过程中（J. Neurosci. Res. 65：463-469，2001）。