Sex Differences in Depressive- and Anxiety-like Behavior in Young Adult Npas4 Heterozygous Mice and Effects on GABAergic and Serotonergic Transmission

Psychology: 4th Place, Honorable Mention (The Ohio State University Denman Undergraduate Research Forum)The regulation of mood and emotional behavior is accomplished by the interconnections of several widespread and complex systems within the brain including the GABAergic and serotonergic systems. . While some of the neurotransmitter pathways underlying depressive and anxiety disorders have been identified, the genetic factors underlying their dysfunctions in affected individuals remain unknown. A possible genetic contributor to GABA (γ-aminobutyric acid) and serotonin (5-HT) deregulations-induced affective disorders is the gene Npas4. To determine whether abnormal expression of Npas4 underlies depressive- and anxiety-like behaviors in a GABAergic or 5-HTergic dependent way, we used male and female Npas4 heterozygotes (HET) and wild type (WT) mice. Behavioral tests were performed in young adult mice and real time quantitative polymerase chain reaction (RT qPCR) was used to assess the expression of the GABA-A α2 and 5-HT1A receptors in the prefrontal cortex (PFC). Female HET mice display increased depressive-like behaviors when compared with female WT mice, while male HET mice display increased anxiety-like behaviors when compared with male WT mice. These data suggest that in young adult mice, Npas4 may contribute more to regulation of anxiety-like behaviors in males and depressive-like behavior in females. In correlation with behavioral data, RT qPCR data show a genotype and sex effect in the expression of GABA-A α2 receptors: HET males have increased receptor expression compared to WT males, while HET females have reduced expression of this receptor compared to WT females. There is a genotype effect for 5HT1A receptors: HET males and females have lower expression of this receptor compared to WT males and females. According to this mouse model, the sex dependent effects of Npas4 on GABA-A and 5-HT receptors expression could contribute to sex differences in mood disorder phenotypes.URO Research Scholar AwardAcademic Major: Neuroscienc