Details

Autor(en) / Beteiligte

• Zhang, Ying
• Cao, Shu-Xia
• Sun, Peng
• He, Hai-Yang
• Yang, Ci-Hang
• Chen, Xiao-Juan
• Shen, Chen-Jie
• Wang, Xiao-Dong
• Chen, Zhong
• Berg, Darwin K
• Duan, Shumin
• Li, Xiao-Ming

Titel

Loss of MeCP2 in cholinergic neurons causes part of RTT- like phenotypes via α7 receptor in hippocampus

Ist Teil von

• Cell research, 2016-06, Vol.26 (6), p.728-742

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Mutations in the X-linked MECP2 gene cause Rett syndrome （RTT）, an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain （BF） eholinergic neurons rather than in the caudate putamen of conditional knockout （Chat-Mecp2-/y） mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2^-/y mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2^-/y mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.