MeCP2 mediates transgenerational transmission of chronic pain.

Progress in neurobiology 2020 Jun

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Pain symptoms can be transmitted across generations, but the mechanisms underlying these outcomes remain poorly understood. Here, we identified an essential role for primary somatosensory cortical (S1) glutamate neuronal DNA methyl-CpG binding protein 2 (MeCP2) in the transgenerational transmission of pain. In a female mouse chronic pain model, the offspring displayed significant pain sensitization. In these mice, MeCP2 expression was increased in S1 glutamate (GluS1) neurons, correlating with increased neuronal activity. Downregulation of GluS1 neuronal MeCP2 in maternal mice with pain abolished offspring pain sensitization, whereas overexpression of MeCP2 in naïve maternal mice induced pain sensitization in offspring. Notably, single-cell sequencing and chromatin immunoprecipitation analysis showed that the expression of a wide range of genes was changed in offspring and maternal GluS1 neurons, some of which were regulated by MeCP2. These results collectively demonstrate the putative importance of MeCP2 as a key regulator in pain transgenerational transmission through actions on GluS1 neuronal maladaptation. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Wenjuan Tao, Changmao Chen, Yuping Wang, Wenjie Zhou, Yan Jin, Yu Mao, Haitao Wang, Likui Wang, Wen Xie, Xulai Zhang, Jie Li, Juan Li, Xiangyao Li, Zhen-Quan Tang, Chenghua Zhou, Zhizhong Z Pan, Zhi Zhang. MeCP2 mediates transgenerational transmission of chronic pain. Progress in neurobiology. 2020 Jun;189:101790