Imbalance towards inhibition as a substrate of aging-associated cognitive impairment.
Imbalance towards inhibition as a substrate of aging-associated cognitive impairment.
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抑制失衡是衰老相关认知障碍的基础。
DOI：
10.1016/j.neulet.2005.11.055
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
DeKoninck,Yves
中科院分区：
文献类型：
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作者：
Wong,TakPan;Marchese,Giorgio;Casu,MariaAntonietta;Ribeiro-da-Silva,Alfredo;Cuello,AClaudio;DeKoninck,Yves
大脑皮层中突触的数量随着年龄的增长而减少。然而，这种结构变化如何转化为在老年动物中观察到的认知障碍仍然未知。就认知表现而言，老年动物并不是一个同质群体；相反，可以使用莫里斯水迷宫等空间记忆任务将他们分为认知未受损的老年组（“正常”）和认知受损的老年组。这两个老年人群提供了前所未有的机会，可以将与认知障碍相关的突触特性与与正常衰老相关的无关因素分开。使用这种分类，我们进行了全细胞膜片钳记录，以测量轰击顶叶皮质中 V 层锥体神经元的基底自发微型兴奋性 (mEPSC) 和抑制性突触电流 (mIPSC)。我们发现，与年轻大鼠相比，老年正常大鼠的 mEPSC 和 mIPSC 频率均较低。相比之下，老年认知障碍大鼠仅表现出 mEPSC 频率降低。这导致抑制失衡，这可能是老年动物认知障碍的重要基础。我们还发现，老年正常大鼠和老年认知障碍大鼠的锥体神经元表现出相似的结构磨损。因此，认知障碍可能更多地与不同神经递质系统之间的平衡改变有关，而不仅仅是突触结构的减少。
The number of synapses in the cerebral cortex decreases with aging. However, how this structural change translates into the cognitive impairment observed in aged animals remains unknown. Aged animals are not a homogenous group with respect to their cognitive performances; but instead, they can be separated into aged cognitively unimpaired (“normal”) and aged cognitively impaired groups using a spatial memory task such as the Morris water maze. These two aged groups provide an unprecedented opportunity to isolate synaptic properties that relate to cognitive impairment from unrelated factors associated with normal aging. Using such classification, we conducted whole-cell patch-clamp recordings to measure basal spontaneous miniature excitatory (mEPSCs) and inhibitory synaptic currents (mIPSCs) bombarding layer V pyramidal neurons in the parietal cortex. We found that the frequencies of both mEPSC and mIPSC were lower in aged normal rats when compared with young rats. In contrast, aged cognitively impaired rats displayed a reduction in mEPSC frequency only. This results in an imbalance towards inhibition that may be an important substrate of the cognitive impairment in aged animals. We also found that pyramidal neurons in both aged normal and aged cognitively impaired rats exhibit similar structural attritions. Thus, cognitive impairment may be more related to an altered balance between different neurotransmitter systems than a mere reduction in synaptic structures.