Endocrine Abstracts

Background: Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. PCOS has been demonstrated to induce depressive-like behavior. Epigenetic alterations such as histone deacetylation (HDAC) and DNA methylation have been suggested in major depression. However, their effects with respect to neuroinflammation are not clear. This study, therefore, investigated the pathogenic role of epigenetic modification in PCOS-associated depression and the therapeutic potential of HDACi, acetate.

Materials and Methods: Adult female Wistar rats (120-150 g) were allotted into groups (n=6/group) namely: control (vehicle; p.o.), acetate-treated (200 mg/kg), letrozole (LET)-treated (1 mg/kg) and LET+Acetate-treated. Letrozole was administered for 21 days to induce PCOS and acetate was administered concomitantly. Biochemical analysis (NF- kB, lipid profile, acetylcholine, malondialdehyde etcetera), gene expression (HDAC2 and DNA methyltransferase), and histological evaluation were performed with appropriate methods.

Results: Treatment with letrozole caused hyperandrogenism, hyperinsulinemia, and disrupted ovarian morphology with evidence of degenerated follicles. In addition, these animals showed depressive-like behavior and increased expression of HDAC2 and DNA methyltransferase in PFC and hippocampal tissues. Biochemical analyses showed elevated NF-kB and acetylcholine levels in PFC and hippocampus as well as plasma lipid peroxidation and impaired antioxidant system in LET-treated animals. Histological analysis of PFC and hippocampus showed neurodegeneration in LET-treated animals compared with control. However, these alterations were attenuated when treated with acetate.

Conclusion: The study demonstrates that PCOS-associated depression is characterized by neuroinflammation and elevated acetylcholine levels, and this is associated with increased expression of HDAC2 and DNA hypermethylation in the PFC and hippocampus. Besides, the study suggests that acetate ameliorates PCOS-associated depression through the suppression of prefrontal and hippocampal DNA methyltransferase and prefrontal but not hippocampal HDAC2 expression.