CLAS: Colby Liberal Arts Symposium

Examination of Schizophrenia-like Symptoms in Rats with a Biallelic Deletion in the Disc1 Gene as a Function of Choline Supplementation

Diamond 221

Schizophrenia is a debilitating, chronic disorder affecting approximately 1% of the population. Research into its neurobiological basis and exploration of novel treatment strategies for it are possible through the use of animal models. In the present study, we used a genetic rat model of schizophrenia to investigate the potential for the essential nutrient, choline, to attenuate behavioral symptoms. Choline is the precursor to the neurotransmitter acetylcholine and is a potent epigenetic factor in development. Accordingly, levels of choline during development exert long-lasting effects on cognition and emotional functioning, both of which are significantly affected in schizophrenia. The genetic rat model used in this study was the biallelic deletion of the Disc1 (disrupted in schizophrenia 1) gene. Abnormalities in this gene are associated with a higher incidence of psychiatric disorders, including schizophrenia. The protective capacity of choline in the model was assessed by comparing wildtype and knockout rats that were treated prenatally with a standard choline diet or a supplemented diet. Key behaviors under investigation were anxiety, exploration, and pre-pulse inhibition. We expected that prenatal choline supplementation would counteract the biallelic deletion of the Disc1 gene, thus stabilizing the abnormal behaviors of the knockout rats. Our preliminary findings revealed little effect on anxiety and exploration. However, the knockout rats displayed significant impairments in pre-pulse inhibition that were rescued by choline supplementation. These results provide excellent evidence that the model reproduces key features of schizophrenia as it occurs in humans and are suggestive of a protective role of early life choline supplementation.

https://digitalcommons.colby.edu/clas/2015/program/87