Can Rett Syndrome Be Cured via Nicotine?

Rett syndrome (RTT) is a rare genetic postnatal neurological disorder of the grey matter of the brain that almost exclusively affects females. It occurs in approximately 1:10,000 live female births in all geographies, and across all races and ethnicities. Currently there is no cure for Rett syndrome.

The research team led by Prof. Li Xiaoming of the School of Medicine, Zhejiang University, pioneered in discovering the role of cholinergic neurons in the cure of Rett syndrome. Relevant findings were published in Cell Research in a paper titled “Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus” on April 22.

The research team 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. They found that choline acetyltransferase expression was reduced in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2−/ymice, 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, their findings suggested that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.