Mons N, Segu L, Nogues X, Buhot M C
Laboratoire de Neurosciences Cognitives, UMR 5106, Avenue des Facultés, 33405 Talence Cedex, France.
Neurobiol Aging. 2004 Sep;25(8):1095-106. doi: 10.1016/j.neurobiolaging.2003.10.014.
Adenylyl cyclase (AC) subtypes have been implicated in memory processes and synaptic plasticity. In the present study, the effects of aging and learning on Ca2+/calmodulin-stimulable AC1, Ca2+-insensitive AC2 and Ca2+/calcineurin-inhibited AC9 mRNA level were compared in the dorsal hippocampus of young-adult and aged C57BL/6 mice using in situ hybridization. Both AC1 and AC9 mRNA expression were downregulated in aged hippocampus, whereas AC2 mRNA remained unchanged, suggesting differential sensitivities to the aging process. We next examined AC mRNA expression in the hippocampus after spatial learning in the Morris water maze. Acquisition of the spatial task was associated with an increase of AC1 and AC9 mRNA levels in both young-adult and aged groups, suggesting that Ca2+-sensitive ACs are oppositely regulated by aging and learning. However, aged-trained mice had reduced AC1 and AC9, but greater AC2, mRNA levels relative to young-trained mice and age-related learning impairments were correlated with reduced AC1 expression in area CA1. We suggest that reduced levels of hippocampal AC1 mRNA may greatly contribute to age-related defects in spatial memory.
腺苷酸环化酶（AC）亚型与记忆过程和突触可塑性有关。在本研究中，使用原位杂交技术比较了年轻和老年C57BL/6小鼠背侧海马中衰老和学习对Ca2+/钙调蛋白刺激的AC1、Ca2+不敏感的AC2和Ca2+/钙调神经磷酸酶抑制的AC9 mRNA水平的影响。老年海马中AC1和AC9 mRNA表达均下调，而AC2 mRNA保持不变，表明对衰老过程的敏感性不同。接下来，我们在莫里斯水迷宫中进行空间学习后检测了海马中AC mRNA的表达。在年轻和老年组中，空间任务的习得均与AC1和AC9 mRNA水平的增加有关，这表明Ca2+敏感的AC受衰老和学习的相反调节。然而，与年轻训练小鼠相比，老年训练小鼠的AC1和AC9 mRNA水平降低，但AC2 mRNA水平更高，并且与年龄相关的学习障碍与CA1区AC1表达降低相关。我们认为，海马AC1 mRNA水平降低可能是导致与年龄相关的空间记忆缺陷的主要原因。
