MeCP2 prevents age-associated cognitive decline via restoring synaptic plasticity in a senescence-accelerated mouse model,Aging Cell

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MeCP2 prevents age-associated cognitive decline via restoring synaptic plasticity in a senescence-accelerated mouse model
Aging Cell ( IF 8.0 ) Pub Date : 2021-08-07 , DOI: 10.1111/acel.13451
Jin-Lan Huang ₁ , Fan Zhang ₂ , Min Su ₁ , Jiaxin Li _{3,

4} , Wen Yi ₁ , Li-Xiang Hou ₁ , Si-Man Yang ₂ , Jin-Yuan Liu ₁ , Hao-An Zhang ₁ , Tengfei Ma _{3,

4} , Deng-Pan Wu ₁

Affiliation

Age-related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl-CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence-accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated-resistant 1 (SAMR1) mice. MeCP2-mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age-related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age-related cognitive decline in neurodegenerative diseases.

中文翻译：

MeCP2 通过在衰老加速小鼠模型中恢复突触可塑性来防止与年龄相关的认知能力下降

阿尔茨海默病 (AD) 等神经退行性疾病中与年龄相关的认知衰退与突触可塑性缺陷有关。因此，探索有希望的目标以增强神经退行性疾病的突触可塑性至关重要。已经证明甲基-CpG 结合蛋白 2 (MeCP2) 在神经元发育中起着至关重要的作用，而 MeCP2 功能障碍会导致各种神经发育障碍。然而，关于 MeCP2 在神经退行性疾病中的作用的报道较少。在研究中，我们发现衰老加速小鼠 P8 (SAMP8) 小鼠的海马体中 MeCP2 表达降低。海马 MeCP2 的过表达可以提高 SAMP8 小鼠的突触可塑性和认知功能，而敲除 MeCP2 会损害衰老加速抗性 1 (SAMR1) 小鼠的突触可塑性和认知功能。MeCP2 介导的突触可塑性调节可能与 CREB1 通路有关。这些结果表明，MeCP2 通过调节突触可塑性在与年龄相关的认知衰退中发挥重要作用，并表明 MeCP2 可能是治疗神经退行性疾病中与年龄相关的认知衰退的有希望的靶点。

更新日期：2021-09-15

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