Aging is associated with the progressive decay of cognitive function. Hippocampus-dependent processes, such as the formation of spatial memory, are particularly vulnerable to aging. Currently, the molecular mechanisms responsible for age-dependent cognitive decline are largely unknown. Here, we investigated the expression and function of the growth arrest DNA damage gamma (Gadd45γ) during aging and cognition. We report that Gadd45γ expression is increased in the hippocampus of aged humans and that Gadd45γ overexpression in the young adult mouse hippocampus compromises cognition. Moreover, Gadd45γ overexpression in hippocampal neurons disrupted cAMP response element-binding protein signaling and the expression of well-established activity-regulated genes. This work shows that Gadd45γ expression is tightly controlled in the hippocampus and its disruption may be a mechanism contributing to age-related cognitive impairments observed in humans.

中文翻译：

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模拟人类年龄相关的 Gadd45γ 表达增加导致年轻成年小鼠的空间识别记忆障碍


衰老与认知功能的逐渐衰退有关。依赖海马体的过程，例如空间记忆的形成，特别容易受到衰老的影响。目前，导致年龄依赖性认知衰退的分子机制在很大程度上尚不清楚。在这里，我们研究了衰老和认知过程中生长停滞 DNA 损伤 γ (Gadd45γ) 的表达和功能。我们报告称，老年人海马体中 Gadd45γ 的表达增加，而年轻成年小鼠海马体中 Gadd45γ 的过度表达会损害认知能力。此外，海马神经元中 Gadd45γ 的过表达破坏了 cAMP 反应元件结合蛋白信号传导以及已确定的活性调节基因的表达。这项工作表明，Gadd45γ 的表达在海马体中受到严格控制，其破坏可能是导致人类观察到的与年龄相关的认知障碍的机制。