Changes in Mll1 effect expression of GAD1 in the brain during development of the prefrontal cortex, reports Journal of Neuroscience paper.
People with schizophrenia may not experience the normal high rates of expression of the GAD1 gene involved in making a chemical messenger in the brain during regular development of the prefrontal cortex, report researchers from University of Massachusetts Medical School and Baylor College of Medicine.
“Studies have yielded strong evidence that schizophrenia involves a decrease in the enzymes, like GAD1, that help make the neurotransmitter GABA. Now we’re starting to identify the mechanisms involved, and our discoveries are pointing to potential new targets for medications,” says NIMH director Thomas R. Insel, M.D.
For genes to be turned on, temporary structural changes in histones must take place to expose the genes’ blueprints in DNA. The researchers found that in schizophrenia changes in Mll1 activity may interfere with this process in histones whose alterations enable the GAD1 blueprint to be exposed. The researchers also showed, in mice, that antipsychotic medications like clozapine appear to correct this epigenetic flaw.
The researchers also found that people with three different variations of the GAD1 gene, variations previously associated with schizophrenia, also were more likely to have indicators of a malfunction in brain development. Among them were indicators of altered epigenetic actions related to GABA synthesis.
The results of the research were published in the October 17 issue of the Journal of Neuroscience.