Chodari Leila, Derafshpour Leila, Jafari Abbas, Ghasemi Maedeh, Mehranfard Nasrin
Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
Brain Res. 2023 Apr 1;1804:148250. doi: 10.1016/j.brainres.2023.148250. Epub 2023 Jan 20.
Hippocampal-dependent memory abilities including spatial memory decline with age. Exercise improves memory decline in aging brain, but, the precise mechanisms are still unknown. Learning and memory are recently hypothesized to be mediated by a β-arrestin (βArr)-dependent β-adrenergic pathway. Hence, we examined the effect of 8 weeks of treadmill exercise on hippocampal expression of β-adrenergic receptors (β-ARs; members of the G protein-coupled receptor family), and βArrs as well as spatial learning and memory in aged male rats to determine whether β-AR/βArr pathway could be involved in age-related memory decline. A total of 24 young (3-month-old) and aged (18-month-old) male Wistar rats were divided into young control, aged sedentary, and aged + exercise (n = 8 for each). Western blot for β1- and β2-ARs as well as βArr1 and βArr2 was performed. Spatial learning and memory were evaluated with the Morris water maze. The results showed significant up-regulation of β1-ARs as well as significant down-regulation of β2-AR and βArrs (βArr1 and βArr2) in the hippocampus of aged rats. Spatial memory, but not spatial learning, was impaired in aging, and treadmill exercise improved it. Notably, the improvement in spatial memory was accompanied by amelioration of β-ARs dysregulation and increase in βArr2 levels after exercise. There was a negative association between the expression of βArr2 and β1-AR, but not β2-AR, such that an increase in βArr2 by exercise was associated with reduced β1-AR expression, suggesting βArr2 may contribute to posttranslational down-regulation of β1-ARs. These data suggest that both G protein-dependent and β-arrestin-dependent β-AR pathways may regulate spatial learning and memory in aging brain.
包括空间记忆在内的海马体依赖性记忆能力会随着年龄增长而下降。运动可改善衰老大脑中的记忆衰退，但其确切机制仍不清楚。最近有研究假设，学习和记忆是由β-抑制蛋白（βArr）依赖性β-肾上腺素能通路介导的。因此，我们研究了8周的跑步机运动对老年雄性大鼠海马体中β-肾上腺素能受体（β-ARs；G蛋白偶联受体家族成员）、βArrs的表达以及空间学习和记忆的影响，以确定β-AR/βArr通路是否与年龄相关的记忆衰退有关。总共24只年轻（3个月大）和老年（18个月大）雄性Wistar大鼠被分为年轻对照组、老年久坐组和老年运动组（每组n = 8）。对β1-ARs、β2-ARs以及βArr1和βArr2进行蛋白质免疫印迹分析。用莫里斯水迷宫评估空间学习和记忆。结果显示，老年大鼠海马体中β1-ARs显著上调，β2-AR和βArrs（βArr1和βArr2）显著下调。衰老会损害空间记忆，但不会损害空间学习能力，跑步机运动可改善空间记忆。值得注意的是，运动后空间记忆的改善伴随着β-ARs失调的改善和βArr2水平的增加。βArr2与β1-AR的表达呈负相关，但与β2-AR无关，因此运动导致的βArr2增加与β1-AR表达降低有关，这表明βArr2可能有助于β1-ARs的翻译后下调。这些数据表明，G蛋白依赖性和β-抑制蛋白依赖性β-AR通路可能都参与调节衰老大脑中的空间学习和记忆。
