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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ase-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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Ase-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

机译：与空间相关的与Ase相关的缺陷与体外海马长时程增强后期的缺陷相关，并被增强cAMP信号通路的药物所减弱

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摘要

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 long- term 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 exhib- ited greater individual differences. Slices from the hippocam- pus 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 attenu- ate 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 sig- naling pathway is defective in age-related spatial memory loss.
机译：为了研究与年龄有关的记忆丧失的生理和分子机制，我们评估了不同年龄组的C57BL / B6小鼠的空间记忆，然后在体外测量了海马长时程增强（L-LTP）的晚期。大多数年幼的老鼠完成了空间任务，而只有少数年老的老鼠完成了空间任务。老龄小鼠不仅犯了更多的错误，而且表现出更大的个体差异。老年小鼠海马切片显示L-LTP显着降低，这与记忆错误显着负相关。因为L-LTP依赖于cAMP的激活，所以我们研究了增强cAMP的药物是否能减轻L-LTP和记忆缺陷。与腺苷酸环化酶正相关的多巴胺D1 / D5受体激动剂和cAMP磷酸二酯酶抑制剂均改善了生理和记忆缺陷，这与cAMP-蛋白激酶A依赖的信号通路存在缺陷的想法一致与年龄有关的空间记忆丧失。

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