DO CHANGES IN SEROTONERGIC NEUROTRANSMISSION UNDERLIE RETINO ID-INDUCED DEPRESSION?

Vitamin A is one of a family of compounds called retinoids. Retinoids are derived from the diet and synthetic sources. During development of the nervous system, retinoids act to regulate nerve cell growth by turning on a subset of neuronal genes. Retinoids are also thought to play an important role in the adult brain but little is known about the behaviours that are influenced by, or what mechanisms might be involved in, retinoid actions. In humans, both excess vitamin A (for example from supplements) and oral retinoid treatments for acne (Roaccutane) have been linked with an increased risk of depression and suicidal behaviour. Serotonin is a neurotransmitter that plays a key role in the control of mood and emotional behaviour. Based on our preliminary data, we predict that retinoids alter the expression of proteins involved in serotonin neurotransmission which causes a reduction in the amount of serotonin available. In humans, impaired serotonin neurotransmission has been suggested to be a cause of depression and many antidepressants work by increasing serotonin levels in the brain. Here we will use a novel mouse model to try to identify whether retinoids can alter serotoninergic neurotransmission in the adolescent brain. These studies will reveal novel mechanisms contributing to depression as well as providing insight into the physiological role for retinoids in the adult brain.