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

Correlation of cognitive performance and morphological changes in neocortical pyramidal neurons in aging.
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DOI:
10.1016/j.neurobiolaging.2010.10.011
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发表时间:
2012-07
影响因子:
4.2
通讯作者:
Ribeiro-da-Silva A
Ribeiro-da-Silva A
中科院分区:
医学2区
文献类型:
--
作者:
Allard S;Scardochio T;Cuello AC;Ribeiro-da-Silva A

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众所周知,大脑皮质在衰老过程中会经历广泛的重塑。在这项研究中,我们使用行为特征的大鼠将年龄相关的形态变化与认知障碍联系起来。为此,在莫里斯水迷宫中对幼年和老年动物进行了测试,以评估它们的认知表现。根据行为特征,动物被灌流,细胞内标记和免疫组织化学相结合的应用。用这种方法,我们描述了皮质锥体神经元的树突形态,以及谷氨酸和GABA能在它们的胞体和树突上的排列模式。我们重点研究了参与Morris水迷宫任务的顶叶皮质(LTPA)和内侧前额叶皮质(MPFC)的关联区。我们发现,老年认知正常动物(AU)和老年认知受损动物(AI)之间存在与年龄相关的树突基底部萎缩。树突棘和谷氨酸能神经元分布从幼年到幼年、从幼年到幼年。另一方面,GABA能结合仅在AU大鼠有减少的趋势。总体而言,这些数据表明,兴奋性/抑制性输入的比率只在人工智能动物中发生了变化。当在交替切片上标记皮质胆碱能静脉曲张时,我们发现与AU或年轻动物相比,AI动物的皮质胆碱能循环也显著减少。在老年动物中,皮质胆碱能曲张的密度与兴奋性/抑制性比率相关。我们的数据表明,胆碱能萎缩和抑制失衡可能是观察到的与年龄相关的行为障碍的原因。
It is well established that the cerebral cortex undergoes extensive remodeling in aging. In this study, we used behaviorally characterized rats to correlate age-related morphological changes with cognitive impairment. For this, young and aged animals were tested in the Morris water maze to evaluate their cognitive performance. Following behavioral characterization, the animals were perfused and a combination of intracellular labeling and immunohistochemistry was applied. Using this approach, we characterized the dendritic morphology of cortical pyramidal neurons as well as the pattern of glutamatergic and GABAergic appositions on their cell bodies and dendrites. We focused on the association region of the parietal cortex (LtPA) and the medial prefrontal cortex (mPFC) for their involvement in the Morris water maze task. We found an age-related atrophy of distal basal dendrites that did not differ between aged cognitively unimpaired (AU) and aged cognitively impaired animals (AI). Dendritic spines and glutamatergic appositions generally decreased from young to AU and from AU to AI rats. On the other hand, GABAergic appositions only showed a trend towards a decrease in AU rats. Collectively, the data show that the ratio of excitatory/inhibitory inputs was only altered in AI animals. When cortical cholinergic varicosities were labeled on alternate sections, we found that AI animals also had a significant reduction of cortical cholinergic boutons compared to AU or young animals. In aged animals, the density of cortical cholinergic varicosities correlated with the excitatory/inhibitory ratio. Our data suggests that both cholinergic atrophy and an imbalance towards inhibition may contribute to the observed age-associated behavioral impairment.
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发表时间: 2009-07-30
期刊: NEURON
影响因子: 16.2
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Deng, Pan-Yue;Xiao, Zhaoyang;Yang, Chuanxiu;Rojanathammanee, Lalida;Grisanti, Laurel;Watt, John;Geiger, Jonathan D.;Liu, Rugao;Porter, James E.;Lei, Saobo
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期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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DOI: 10.1016/j.neurobiolaging.2005.09.034
发表时间: 2006-11-01
影响因子: 4.2
作者:
Bell, Karen F. S.;Ducatenzeiler, Adriana;Cuello, A. Claudio
通讯作者: Cuello, A. Claudio
DOI: 10.1152/jn.1998.80.6.3383
发表时间: 1998-12-01
影响因子: 2.5
作者:
Frerking, M;Malenka, RC;Nicoll, RA
通讯作者: Nicoll, RA
DOI: 10.1523/jneurosci.1508-04.2004
发表时间: 2004-09-15
影响因子: 5.3
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Bruno, MA;Clarke, PBS;Saragovi, HU
通讯作者: Saragovi, HU