Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway
Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway
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DOI：
10.1073/pnas.96.9.5280
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Bach, ME;Barad, M;Kandel, ER
为了研究年龄相关记忆丧失的生理和分子机制，我们对不同年龄组C57BL/B6小鼠的空间记忆进行了评估，并在体外测量了海马长期增强（L-LTP）的后期阶段。大多数年轻小鼠获得了空间任务，而只有少数老年小鼠获得了空间任务，老年小鼠不仅出现了更多的错误，而且表现出更大的个体差异。老年小鼠海马切片显示L-LTP显著降低，这与记忆错误呈显著负相关。由于L-LTP依赖于cAMP的激活，我们研究了增强cAMP的药物是否会减轻L-LTP和记忆缺陷。多巴胺D1/D5受体激动剂（与腺苷酸环化酶正偶联）和cAMP磷酸二酯酶抑制剂都能改善生理和记忆缺陷，这与cAMP蛋白激酶a依赖的信号通路在年龄相关的空间记忆丧失中存在缺陷的观点一致。
To study the physiological and molecular mechanisms of age-related memory loss, we assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured in vitro the late phase of hippocampal longterm potentiation (L-LTP), Most young mice acquired the spatial task, whereas only a minority of aged mice did, Aged mice not only made significantly more errors but also exhibited greater individual differences, Slices from the hippocampus of aged mice exhibited significantly reduced L-LTP, and this was significantly and negatively correlated with errors in memory. Because L-LTP depends on cAMP activation, we examined whether drugs that enhanced cAMP would attenuate the L-LTP and memory defects, Both dopamine D1/D5 receptor agonists, which are positively coupled to adenylyl cyclase, and a cAMP phosphodiesterase inhibitor ameliorated the physiological as well as the memory defects, consistent with the idea that a cAMP-protein kinase A-dependent signaling pathway is defective in age-related spatial memory loss.