Faculty Mentor(s)

Dr. Leah Chase, Biology and Chemistry

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We have previously demonstrated that early post-natal exposure of rat pups to the NMDA receptor agonist, homocysteic acid (HCA) from P3-P21 leads to the development of mixed manic/depressive behaviors following puberty. The manic behaviors are effectively reversed by lithium treatment, and the depressive behaviors are reversed by acute ketamine treatment. Thus, HCA appears to induce a bipolar-like phenotype in rats. The goal of this study was to determine whether HCA exposure also induces gene expression changes that are consistent with a bipolar phenotype. Microarray analyses were performed on tissue obtained from the prefrontal cortices of saline- and HCA-treated rats at 3 weeks and 32-weeks of age. At 3 weeks, HCA rats exhibited 132 differentially expressed genes relative to control, many of which suggest there is a delay in oligodendrocyte development. Interestingly, several genes that have been identified as exhibiting reduced expression in bipolar disorder and schizophrenia, including MBP, PLP1, MAG, MOG, ERMN, and GSN. At 32-weeks, 316 differentially expressed genes were identified, including many genes which are associated with GABAergic interneuron function or regulate excitatory/inhibitory balance including SST, PVLB, GABRB2, GABRA6, KCNA1. We confirmed several of these alterations in gene expression using qPCR. Collectively, these results suggest that HCA treatment leads to changes in gene expression that mirror those previously identified in GWAS and microarray studies in post-mortem BD patients.


This research was supported by the Hope College Neuroscience Program and Schaap Endowed Funds for Undergraduate Research.