Synaptic Alterations in the Cerebral Cortex during Aging

衰老过程中大脑皮层的突触变化

• 批准号: 6943016
• 负责人: A CLAUDIO CUELLO
• 金额: $ 26.19万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943016
• 关键词: aging; cerebral cortex; electron microscopy; electrophysiology; immunocytochemistry; laboratory rat; light microscopy; memory disorders; neocortex; neural transmission; neuroanatomy; neurons; neuroprotectants; pyramidal cells; single cell analysis; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): The aging process in the human species leads to the deterioration of higher CNS functions. Age-related changes experienced by cerebral cortex neurons and their synapses are at the heart of these cognitive deficiencies observed in the old age. There is, however, scanty experimental data defining which neocortical neurons and which synapses are most affected structurally or functionally and in which temporal sequence. This project will test the hypothesis that 1) large pyramidal neurons are more sensitive than non-pyramidal cortical neurons to the aging process and that 2) an imbalance between excitatory and inhibitory influences upon pyramidal neurons might exist in the neocortex of cognitively impaired aged individuals. To test the above hypotheses a multidisciplinary team will apply a combination of behavioral, physiological (single cell electrophysiological, patch clamp) and morphological (light and electron microscopy immunocytochemistry of intracellularly labeled neurons) studies to define which particular cerebral cortex neurons are most affected with aging, what is their synaptic pattern and whether an imbalance between excitatory and inhibitory synaptic discharges occur in memory impaired aged animals when compared with aged non-impaired animals. This research should reveal which neuronal and transmitter-specific synaptic systems are more vulnerable to the aging process, thus providing valuable clues for their protection and/or corrective pharmacological treatments.

描述（由申请人提供）：人类物种的衰老过程导致较高的中枢神经系统功能的恶化。脑皮质神经元及其突触经历的与年龄相关的变化是这些认知缺陷在老年中观察到的核心。但是，存在稀少的实验数据，这些数据定义了哪些新皮质神经元和突触在结构或功能上以及在哪些时间序列上受到最大影响。该项目将检验以下假设：1）大型锥体神经元比非锥体皮质神经元更敏感的对衰老过程的敏感性，而2）兴奋性和抑制性影响对锥体神经元的不平衡可能存在于认知障碍的新生儿中。要测试上述假设的多学科团队将采用行为，生理学（单细胞电生理学，斑块夹）和形态学（光和电子显微镜免疫细胞内神经元的免疫细胞化学）的组合与年迈的非受损动物相比，记忆力障碍动物的记忆障碍中发生突触放电。这项研究应揭示哪些神经元和发射器特异性突触系统更容易受到衰老过程，从而为其保护和/或纠正药理治疗提供了宝贵的线索。

项目成果

Imbalance towards inhibition as a substrate of aging-associated cognitive impairment.

抑制失衡是衰老相关认知障碍的基础。

• DOI: 10.1016/j.neulet.2005.11.055
• 发表时间: 2006
• 期刊: Neuroscience letters.
• 作者: Wong,TakPan;Marchese,Giorgio;Casu,MariaAntonietta;Ribeiro-da-Silva,Alfredo;Cuello,AClaudio;DeKoninck,Yves
• 通讯作者: DeKoninck,Yves

Correlation of cognitive performance and morphological changes in neocortical pyramidal neurons in aging.

• DOI: 10.1016/j.neurobiolaging.2010.10.011
• 发表时间: 2012-07
• 期刊: Neurobiology of aging
• 影响因子: 4.2
• 作者: Allard S;Scardochio T;Cuello AC;Ribeiro-da-Silva A
• 通讯作者: Ribeiro-da-Silva A