Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex.
Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex.
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DOI：
10.3389/fnagi.2021.656944
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发表时间：
2021
影响因子：
4.8
通讯作者：
Helmstetter FJ
中科院分区：
文献类型：
--
作者：
Dulka BN;Trask S;Helmstetter FJ
衰老的标志是受损和修饰的脑蛋白质的积累，而泛素-蛋白酶体系统（UPS）对细胞蛋白质降解很重要。最近的工作已经确定了UPS在记忆和突触可塑性中的关键作用，但UPS在与年龄相关的认知衰退中的作用仍然知之甚少。本研究采用微量恐惧条件反射（TFC）对青年、中年和老年雄性和雌性大鼠进行训练，探讨年龄和性别对记忆的影响。然后，我们使用蛋白质印迹法测量UPS相关蛋白降解的标志物（Rpt 6蛋白酶体调节亚基的磷酸化和K48连接的多聚泛素化）。我们发现，老年男性，而不是老年女性，表现出行为缺陷的记忆检索。老年男性还显示减少磷酸化的Rpt 6蛋白酶体亚基和积累的K48在基底外侧杏仁核，而老年女性表现出类似的模式，在内侧前额叶皮质。这些研究结果表明，UPS功能的标志物不同的影响，年龄和性别的大脑区域依赖性的方式。总之，这些结果提供了一个重要的一步，了解UPS和电路水平的差异，在老年男性和女性。
Aging is marked by an accumulation of damaged and modified brain proteins, and the ubiquitin-proteasome system (UPS) is important for cellular protein degradation. Recent work has established a critical role for the UPS in memory and synaptic plasticity, but the role of the UPS in age-related cognitive decline remains poorly understood. We trained young, middle-aged, and aged male and female rats using trace fear conditioning (TFC) to investigate the effects of age and sex on memory. We then measured markers of UPS-related protein degradation (phosphorylation of the Rpt6 proteasome regulatory subunit and K48-linked polyubiquitination) using western blots. We found that aged males, but not aged females, showed behavioral deficits at memory retrieval. Aged males also displayed reduced phosphorylation of the Rpt6 proteasome subunit and accumulation of K48 in the basolateral amygdala, while aged females displayed a similar pattern in the medial prefrontal cortex. These findings suggest that markers of UPS function are differentially affected by age and sex in a brain region-dependent manner. Together these results provide an important step toward understanding the UPS and circuit-level differences in aging males and females.
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影响因子：
10.6
作者：
Gruene TM;Roberts E;Thomas V;Ronzio A;Shansky RM
通讯作者：
Shansky RM
DOI：
10.1523/jneurosci.4427-11.2012
发表时间：
2012-04-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Djakovic SN;Marquez-Lona EM;Jakawich SK;Wright R;Chu C;Sutton MA;Patrick GN
通讯作者：
Patrick GN
影响因子：
15.9
作者：
Gilmartin MR;Balderston NL;Helmstetter FJ
通讯作者：
Helmstetter FJ
影响因子：
2
作者：
Gilmartin, Marieke R.;Helmstetter, Fred J.
通讯作者：
Helmstetter, Fred J.
影响因子：
7.7
作者：
Gruene, Tina M.;Flick, Katelyn;Shansky, Rebecca M.
通讯作者：
Shansky, Rebecca M.