Open AccessSubstantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities
Author(s) -
Hiroyasu Murasawa,
Hiroyuki Kobayashi,
Jun Imai,
Takahiko Nagase,
Hitomi Soumiya,
Hidefumi Fukumitsu
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0258830
Subject(s) - mecp2 , rett syndrome , endocrinology , medicine , biology , neurotrophic factors , brain derived neurotrophic factor , neuroscience , phenotype , genetics , gene , receptor
Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 ( MECP2 ) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats ( Mecp2 +/− ) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%–50%) in multiple brain regions compared to female Mecp2 +/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2 -deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.