Epilepsy drug contributes to sleep loss

A new study, published in Molecular Psychiatry, has found that the enzyme GABA transaminase, which is targeted by some epilepsy drugs, contributes to sleep loss. 

These findings from the mutant fruitfly research called sleepless (sss) could offer more insight into the relationship between sleep disruption and some neurological disorders. It is hoped that by better understanding this connection, patients could receive treatment that controls both symptoms.

The research was led by Dr Amita Sehgal, head of the Chronobiology Program at the University of Pennsylvania's Perelman School of Medicine. Dr Seghal, along with a team, looked at the proteomics of the sss mutant brain and found that GABA transaminase is increased in the sss brain compared to controls. The enzyme breaks down GABA, so the levels in the brain are lower and, as GABA promotes sleep, there was a loss of sleep in the mutant fly.

Dr Seghal said: "Epilepsy is essentially an increase-in-firing disorder of the brain and maybe a decrease in activity of the neurotransmitter GABA, too."

The lead researcher, who is also a professor of Neuroscience, said that changes in GABA transaminase activity are implicated in epilepsy and some other psychiatric disorders, which could account for some associated sleep problems.

However, the relationship between the sss protein and GABA is not fully understood. The protein controls neural activity, causing neural firing when it isn't present, which is likely to use up a lot of energy, according to Dr Sehgal.

GABA transaminase works in the mitochondria, the energy-production organelle in the glial cells of the brain, which provide fuel for neurons. The neural firing triggers a high demand of energy in sss brains and could alter the mitochondrial metabolism, including GABA transaminase function in glia.

Previous research by Dr Seghal had showed that sss also affects the acetylcholine receptors, which could also cause an inability to sleep. As well as this, an increased energy demands on glia, which increase GABA transaminase and decrease GABA, may also cause sleep loss. In contrast, if GABA is increased, then sleep is increased, as in flies that lack GABA transaminase.