| First Author | Zhang Y | Year | 2016 |
| Journal | Cell Res | Volume | 26 |
| Issue | 6 | Pages | 728-42 |
| PubMed ID | 27103432 | Mgi Jnum | J:278033 |
| Mgi Id | MGI:6356087 | Doi | 10.1038/cr.2016.48 |
| Citation | Zhang Y, et al. (2016) Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via alpha7 receptor in hippocampus. Cell Res 26(6):728-42 |
| abstractText | 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) cholinergic 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 alpha7 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. |
