前脑I型腺苷酸环化酶的过表达会损害老年小鼠而非年轻小鼠的空间记忆。
Overexpression of type I adenylyl cyclase in the forebrain impairs spatial memory in aged but not young mice.
作者信息
Garelick Michael G, Chan Guy C K, DiRocco Derek P, Storm Daniel R
机构信息
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
出版信息
J Neurosci. 2009 Sep 2;29(35):10835-42. doi: 10.1523/JNEUROSCI.0553-09.2009.
Abstract
Hippocampus-dependent memory requires a cAMP signal that is generated by Ca2+-stimulated adenylyl cyclases (AC1, AC8). Young transgenic mice overexpressing AC1 in the forebrain (AC1+ mice) have enhanced hippocampal long-term potentiation, superior memory for novel object recognition and more persistent remote contextual memory. To determine whether increasing AC1 expression improves memory when older mice are trained, we analyzed fear, recognition, and spatial memory in mice aged to 25 months. Here we report that young adult AC1+ mice have enhanced social recognition memory, and normal fear and spatial memory. Surprisingly, aged AC1+ mice had poorer spatial memory than age-matched wild-type littermates. These data suggest that the decrease in Ca2+-stimulated adenylyl cyclase activity during aging of wild-type mice may be an adaptive mechanism required to maintain spatial memory function.
摘要
海马体依赖的记忆需要由钙刺激的腺苷酸环化酶（AC1、AC8）产生的环磷酸腺苷（cAMP）信号。在前脑过度表达AC1的年轻转基因小鼠（AC1+小鼠）具有增强的海马体长时程增强效应、对新物体识别的卓越记忆以及更持久的远程情境记忆。为了确定在老年小鼠接受训练时增加AC1表达是否能改善记忆，我们分析了25月龄小鼠的恐惧、识别和空间记忆。我们在此报告，年轻成年AC1+小鼠具有增强的社会识别记忆，以及正常的恐惧和空间记忆。令人惊讶的是，老年AC1+小鼠的空间记忆比年龄匹配的野生型同窝小鼠更差。这些数据表明，野生型小鼠衰老过程中钙刺激的腺苷酸环化酶活性的降低可能是维持空间记忆功能所需的一种适应性机制。
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