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

Abstract

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.

• Authors: Jin-Lan Huang, Fan Zhang, Min Su, Jiaxin Li, Wen Yi, Li-Xiang Hou, Si-Man Yang, Jin-Yuan Liu, Hao-An Zhang, Tengfei Ma, Deng-Pan Wu
• Journal: Aging cell (Aging Cell) Vol. 20 Issue 9 Pg. e13451 (09 2021) ISSN: 1474-9726 [Electronic] England
• PMID: 34363729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Chemical References

• Mecp2 protein, mouse
• Methyl-CpG-Binding Protein 2

Topics

• Age Factors
• Animals
• Cellular Senescence
• Cognition
• Cognitive Dysfunction (genetics, metabolism, pathology)
• Disease Models, Animal
• Hippocampus (metabolism, pathology)
• Methyl-CpG-Binding Protein 2 (genetics, metabolism)
• Mice
• Neuronal Plasticity