Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

Medical Epigenetics, Journal Year: 2016, Volume and Issue: 4(1), P. 1 - 19

Published: March 23, 2016

Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as animal model for psychosis since the discovery that reelin is 50% down-regulated postmortem psychotic brain. Brain abnormalities +/rl are similar to brain include reduction glutamic acid de carboxylase 67 (GAD67), dendritic arbors spine density cortex hippocampus, function including long-term potentiation (LTP). In spite these abnormalities, behavioral subtle controversial. Recent findings indicate (RELN) GAD67 promoters hypermethylated neurons DNA methyltransferase 1 (DNMT1) up-regulated. Hypermethlyation RELN can be induced treating mice with methionine, display +/rl. Thus, combines genetic heterozygocity epigenesis holds promise understanding Reelin down-regulation psychosis.

Language: Английский

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