N-3 Polyunsaturated Fatty Acids Attenuated Postpartum Depression Through MicroRNA-regulated Neuroendocrinergic and Serotonergic Mechanisms (P08-118-19)

Abstract

Abstract Objectives The purpose of the present study was to investigate the hypothesis that n-3 polyunsaturated fatty acids (PUFAs) had antidepressant effects through microRNA (miR)-regulated neurobiological systems in dams with postpartum depression (PPD) induced by pup separation (PS). Methods After mating, the female rats were fed a modified AIN-93 G diet with 0% or 1% n-3 PUFAs relative to total energy intake during gestation and lactation periods. After birth, dams were separated from their pups for 15 min (control) or 180 min (PS) every day on postpartum day 2–14. There were four groups (n = 8/group): control, PS, n-3 PUFAs and PS + n-3 PUFAs. Results PS increased latencies to contact first pup and to retrieve all pup increased immobility but decreased climbing during forced swimming test, and decreased sucrose preference. PS increased activity of hypothalamic-pituitary-adrenal (HPA) axis including expression of corticotrophin releasing factor and glucocorticoid receptor, and levels of adrenocorticotropic hormone and corticosterone. PS also decreased serotonergic neurotransmission including expressions of cAMP response element binding protein (CREB), pCREB, brain-derived neurotrophic factor (BDNF) and serotonin 1A receptor, and level of serotonin. In addition, PS increased inflammation including expressions of TNF-α, IL-6, PGE2, and N-methyl-D-aspartate receptor (NMDAR) 2B. PS modified HPA-axis, serotonergic neurotransmission, inflammation and NMDAR 2B through miR-218, miR-132, miR-182 and miR-155. N-3 PUFAs modified depressive behaviors, HPA axis activity, serotonergic neurotransmission, inflammation through miR-218, miR-182 and miR-155. However, n-3 PUFAs had no effect on miR-17, miR-132, and NMDAR 2B. Conclusions The present study suggested that the antidepressant-like effects of n-3 PUFAs could be due to regulation of HPA axis activity, serotonergic neurotransmission and inflammation via miR-218, miR-182 and miR-155, rather than NMDAR. Funding Sources This work was supported by the National Research Foundation of Korea grant funded by the Korea government (NRF-2018R1A2B6002486).