Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment.
Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment.
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DOI：
10.1523/jneurosci.6410-09.2010
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发表时间：
2010-06-02
期刊：
影响因子：
--
通讯作者：
Morrison JH
中科院分区：
文献类型：
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作者：
Dumitriu D;Hao J;Hara Y;Kaufmann J;Janssen WG;Lou W;Rapp PR;Morrison JH
记忆障碍相关的记忆障碍（AAMI）发生在包括人类在内的许多哺乳动物物种中。与通过神经元死亡发生回路中断的阿尔茨海默病（AD）相反，AAMI是由于在没有显著神经元损失的情况下的回路和突触中断，因此可能更适合预防或治疗。我们研究了年龄对年轻和老年雄性和雌性恒河猴（Macaca mulatta）背外侧前额叶皮层第III层46区锥体神经元和突触密度的影响，通过延迟非匹配样本（DNMS）和延迟反应（DR）任务测试认知状态。认知测试显示，在DNMS的收购和性能与年龄相关的递减。我们的形态计量学分析揭示了锥体细胞上与年龄相关的棘丢失（33%，p< 0.05）和46区III层轴棘突触密度降低（32%，p<0.01）。此外，脊柱类型的分布也发生了与年龄相关的变化，反映出小而薄的脊柱的选择性脆弱性，这些脊柱被认为特别具有可塑性，并与学习有关。虽然动物的突触密度和总体脊柱尺寸平均值都预测了获得DNMS所需的试验次数（即，学习任务），行为的最强相关性被发现是薄刺的头部体积，行为和蘑菇刺的大小或密度之间没有相关性。一旦学习了任务，没有突触指数与记忆表现相关。
Age-associated memory impairment (AAMI) occurs in many mammalian species including humans. In contrast to Alzheimer’s disease (AD) where circuit disruption occurs through neuron death, AAMI is due to circuit and synapse disruption in the absence of significant neuron loss and thus may be more amenable to prevention or treatment. We have investigated the effects of aging on pyramidal neurons and synapse density in Layer III of area 46 in dorsolateral prefrontal cortex of young and aged, male and female Rhesus monkeys (Macaca mulatta) that were tested for cognitive status through the delayed non-matching-to-sample (DNMS) and delayed response (DR) tasks. Cognitive tests revealed an age-related decrement in both acquisition and performance on DNMS. Our morphometric analyses revealed both an age-related loss of spines (33%, p< 0.05) on pyramidal cells and decreased density of axo-spinous synapses (32%, p<0.01) in layer III of area 46. In addition, there was an age-related shift in the distribution of spine types reflecting a selective vulnerability of small, thin spines, thought to be particularly plastic and linked to learning. While both synapse density and the overall spine size average of an animal were predictive of number of trials required for acquisition of DNMS (i.e., learning the task), the strongest correlate of behavior was found to be the head volume of thin spines, with no correlation between behavior and mushroom spine size or density. No synaptic index correlated with memory performance once the task was learned.