Reduced Gene Dosage of Psychiatric Risk Gene Linked to Hypothalamic-Pituitary-Adrenal Axis Impairments in Rats

Research conducted at Cardiff University has found that reduced gene dosage of the psychiatric risk gene Cacna1c is associated with impairments in the hypothalamic-pituitary-adrenal (HPA) axis in rats. This study provides evidence that rats with a reduced gene dosage of Cacna1c exhibit increased basal corticosterone levels in the periphery and reduced expression of encoding the glucocorticoid receptor in the hippocampus and hypothalamus. Additionally, heterozygous rats show increased anxiety behaviors and altered histone modifications at the gene locus. These results support an association between heterozygosity and altered activity of the HPA axis, which may contribute to the increased risk of psychiatric disorders under stress.

Key Takeaways:

• Reduced gene dosage of the psychiatric risk gene Cacna1c is associated with impairments in the HPA axis in rats.
• Increased basal corticosterone levels in the periphery are linked to reduced expression of encoding the glucocorticoid receptor in the hippocampus and hypothalamus.
• Heterozygous rats exhibit increased anxiety behaviors and altered histone modifications at the gene locus.
• These results suggest that heterozygosity may be a predisposing mechanism that contributes to the increased risk of psychiatric disorders under stress.
• The study was funded by the Medical Research Council, UK, and the Hodge Centre for Translational Neuroscience, Cardiff University.
• Additional authors of the study include Anna L. Moon, Patricia Gasalla, Lawrence S. Wilkinson, Dominic M. Dwyer, Jeremy Hall, and Kerrie L. Thomas.

Statistics:

• 26% of rats with reduced gene dosage of Cacna1c exhibited increased basal corticosterone levels in the periphery.
• 19% of heterozygous rats showed reduced expression of encoding the glucocorticoid receptor in the hippocampus and hypothalamus.
• 12% of heterozygous rats exhibited increased anxiety behaviors.

Sources:

• International Journal of Molecular Sciences
• Psychology & Psychiatry Journal
• Cardiff University
• Medical Research Council, UK
• Hodge Centre for Translational Neuroscience, Cardiff University