Aggro fruit flies may hold genetic keys to human mental illness

Scientists are creeping closer to the genetic mechanisms that underpin schizophrenia and bipolar disorder through inducing aggression in fruit flies.

A team led by Liesbeth Zwarts of Belgium’s University of Leuven are studying how altered levels of a protein associated with a gene thought to be linked to mental illness affects behaviour.

In humans, mutations of the gene known as PRODH, situated on chromosome 22, has been associated with the development of schizophrenia, bipolar disorder and some other, rarer, neurological conditions. Its influence has been confirmed in mouse studies, but the precise mechanisms by which it works have remained little understood.

To try to throw some light on the subject, Zwarts and her colleagues looked at the role of an almost identical fruit fly gene, known as slgA.

In a previous study, in 2008, the team had established that neutralising slgA induced aggressive behaviour in fruit flies. Manipulating levels and different proteins expressed by the gene (known as isoforms) thus made for a promising avenue into understanding the functions that underpin the sort of aggression that often typifies mental illness in humans.

Reporting in the journal Disease Models and Mechanisms, the scientists reveal that although slgA is found throughout the fruit fly brain, only the slgA found in an area known as the lateral neurons ventral (LNv) produced aggression when manipulated.

The results suggest that particular behaviours maybe linked to protein components in specific cell types, and that disruption to the metabolism of those specific types may be what catalyses abnormal behaviour.

Interestingly, the lateral neurons ventral are also known to play a key role in regulating circadian rhythms, which determine the sleep/wake cycle – in flies and humans both.

Disruption to circadian rhythms has previously been identified as a driver for neurological disorders. However, Zwarts and her colleagues established that changing the activity of the slgA gene did not affect the cells’ circadian regulation.

Thus, the lateral neurons ventral may affect mental health in at least two – although separate – ways.

The team plans to continue its investigation, using the fruit fly model to assist in determining why current treatments for neuropsychiatric disorders in humans don’t always work.

“Once we have demonstrated the direct relevance of our Drosophila models for psychiatric disorders, we aim to pursue drug screens,” says team member Patrick Callaerts.

“In that sense our work may contribute to defining alternative treatment options.”