Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability
Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability
复制标题
DOI：
10.1016/j.expneurol.2008.01.016
复制
发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Brunso-Bechtold, Judy K.
中科院分区：
文献类型：
--
作者：
Adams, Michelle M.;Shi, Lei;Brunso-Bechtold, Judy K.
热量限制（CR）是指每日减少总热量摄入，而不减少微量营养素或不成比例地减少任何一种饮食成分。CR可以可靠地增加各种物种的寿命，并似乎可以抵消整个身体衰老过程的某些方面。对大脑的影响尚不清楚，但中度CR似乎可以减轻与年龄相关的认知能力下降。因此，我们确定了年龄和CR对海马CA 3区关键突触蛋白的影响，以及这些变化是否与海马依赖性学习和记忆任务的行为差异相关。我们观察到N-甲基-D-天冬氨酸（NMDA）型的NR 1、N2 A和N2 B亚基以及α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型离子型谷氨酸受体的GluR 1和GluR 2亚基的总体年龄相关性下降。有趣的是，我们发现，与年轻AL动物相比，CR最初降低谷氨酸受体亚单位水平，然后在整个生命周期内稳定该水平。突触体蛋白，一种突触前囊泡蛋白，也表现出类似的模式。我们还发现，CR和随意（AL）喂养的动物在Morris水迷宫任务中表现出与年龄相关的认知能力下降。然而，AL动物在青年和中年之间以及中年和老年之间下降，而CR大鼠仅在青年和中年之间下降。因此，CA 3中关键突触蛋白的减少和整个寿命期间发生的认知下降通过CR稳定。这种年龄相关的减少和CR诱导的稳定可能会影响CA 3突触可塑性，从而影响海马功能。爱思唯尔公司出版
Caloric restriction (CR) is a daily reduction of total caloric intake without a decrease in micronutrients or disproportionate reduction of any one dietary component. CR can increase lifespan reliably in a wide range of species and appears to counteract some aspects of the aging process throughout the body. The effects on the brain are less clear, but moderate CR seems to attenuate age-related cognitive decline. Thus, we determined the effects of age and CR on key synaptic proteins in the CA3 region of the hippocampus and whether these changes were correlated with differences in behavior on a hippocampal-dependent learning and memory task. We observed an overall, age-related decline in the NR1, N2A and N2B subunits of the N-methyl-D-aspartate (NMDA)-type and the GluR1 and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-type ionotropic glutamate receptors. Interestingly, we found that CR initially lowers the glutamate receptor subunit levels as compared to young AL animals, and then stabilizes the levels across lifiespan. Synaptophysin, a presynaptic vesicle protein, showed a similar pattern. We also found that both CR and ad libitum (AL) fed animals exhibited age-related cognitive decline on the Morris water maze task. However, AL animals declined between young and middle age, and between middle age and old, whereas CR rats only declined between young and middle age. Thus, the decrease in key synaptic proteins in CA3 and cognitive decline occurring across lifespan are stabilized by CR. This age-related decrease and CR-induced stabilization are likely to affect CA3 synaptic plasticity and, as a result, hippocampal function. Published by Elsevier Inc.