People with the inherited disorder myotonic dystrophy (DM) often experience excessive daytime sleepiness and fatigue, as well as altered responses to anesthetics that can put them at risk for complications when hospitalized.

Emory researchers, in collaboration with colleagues at Columbia and University of Florida, now have evidence from a mouse model of DM’s central nervous system symptoms, indicating a link to the inhibitor neurotransmitter GABA — and a potential remedy.

The results are published in eNeuro.

“Problems with sleep and anesthetic responses are two major concerns for people with myotonic dystrophy,” says Gary Bassell, PhD, chair of cell biology at Emory University School of Medicine. “The behavioral, pharmacologic and molecular alterations we’ve uncovered help us understand where those aspects of the disorder come from.”

The lead author of the paper is Kamyra Edokpolor, PhD, a former Emory graduate student, with contributions from anesthesiologist Paul Garcia’s lab at Columbia and neurogeneticist Eric Wang’s lab at University of Florida.

The eNeuro paper describes how the DM model mice have enhanced sensitivity to GABA. They display a stronger response to benzodiazepines, a class of anti-anxiety and anti-insomnia drugs that act through GABA. Additional findings suggest that drugs that counteract benzodiazepines, such as the repurposed antidote flumazenil, might work against DM’s prolonged sleep and daytime sleepiness.

Source: Read Full Article