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）：人类的衰老过程会导致高级中枢神经系统功能的退化。大脑皮层神经元及其突触经历的与年龄相关的变化是老年人观察到的这些认知缺陷的核心。然而，很少有实验数据来定义哪些新皮层神经元和突触在结构或功能上受到最大影响，以及在哪个时间序列中受到影响。本项目将验证以下假设：1)大锥体神经元比非锥体皮质神经元对衰老过程更敏感；2)认知障碍老年人新皮层中锥体神经元可能存在兴奋性和抑制性影响之间的不平衡。为了验证上述假设，一个多学科团队将结合行为学、生理学（单细胞电生理学、膜片钳）和形态学（细胞内标记神经元的光镜和电子显微镜免疫细胞化学）研究来确定哪些特定的大脑皮层神经元受衰老影响最大。它们的突触模式是什么？与未受损的老年动物相比，记忆受损的老年动物是否存在兴奋性和抑制性突触放电的不平衡。这项研究将揭示哪些神经元和递质特异性突触系统更容易受到衰老过程的影响，从而为它们的保护和/或纠正性药物治疗提供有价值的线索。

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