Department of Psychology, The University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, WI 53201, USA.
Int J Mol Sci. 2020 Jul 28;21(15):5352. doi: 10.3390/ijms21155352.
Aging is associated with cognitive decline, including impairments in the ability to accurately form and recall memories. Some behavioral and brain changes associated with aging are evident as early as middle age, making the understanding of associated neurobiological mechanisms essential to aid in efforts aimed at slowing cognitive decline throughout the lifespan. Here, we found that both 15-month-old and 22-month-old rats showed impaired memory recall following trace fear conditioning. This behavioral deficit was accompanied by increased zif268 protein accumulation relative to 3-month-old animals in the medial prefrontal cortex, the dorsal and ventral hippocampi, the anterior and posterior retrosplenial cortices, the lateral amygdala, and the ventrolateral periaqueductal gray. Elevated zif268 protein levels corresponded with decreases in phosphorylation of the Rpt6 proteasome regulatory subunit, which is indicative of decreased engagement of activity-driven protein degradation. Together, these results identify several brain regions differentially impacted by aging and suggest that the accumulation of proteins associated with memory retrieval, through reduced proteolytic activity, is associated with age-related impairments in memory retention.
衰老是与认知能力下降相关的,包括在准确形成和回忆记忆方面的障碍。一些与衰老相关的行为和大脑变化早在中年就很明显,因此了解相关的神经生物学机制对于帮助减缓整个生命周期的认知能力下降至关重要。在这里,我们发现,15 个月大和 22 个月大的大鼠在痕迹恐惧条件反射后表现出记忆回忆受损。这种行为缺陷伴随着内侧前额叶皮层、背侧和腹侧海马体、前和后后顶叶皮层、外侧杏仁核和腹外侧导水管周围灰质中相对于 3 个月大的动物的 zif268 蛋白积累增加。Rpt6 蛋白酶体调节亚基磷酸化水平降低与 zif268 蛋白水平升高相对应,这表明活性驱动的蛋白降解的参与减少。总的来说,这些结果确定了几个受衰老影响不同的大脑区域,并表明与记忆检索相关的蛋白质的积累,通过降低蛋白水解活性,与年龄相关的记忆保留障碍有关。