The effect of maternal depression on the development of hypothalamic neuroinflammation in rat pups

Maternal depression that develops during pregnancy and after delivery is defined as an important public health problem. Maternal depression negatively affects the health and quality of life of both the mother and the offspring. The etiology of major depressive disorder is extremely complex and not fully elucidated. Neuroinflammation is considered as a widely accepted hypothesis in the etiology of depression. In this thesis project, it was aimed to evaluate the effects of neuroinflammation-related kynurenine pathway metabolites on hypothalamic gene expression in first generation offspring of rats with experimental maternal depression model. A chronic mild stress model (CHS) was applied on pregnant rats. The hypothalamus tissues of the offspring of the control (C), sertraline (S), depression (D) and depression+sertraline (D+S) group pregnant rats on postnatal 1, 30 and 150 days were taken. After total RNA isolation, cDNA synthesis was performed. The expression levels of kynurenine pathway, pro- and anti-inflammatory cytokine genes (IDO1, HAAO, AADAT, KMO, IL1β, IL6, TNFα, TGFβ and IL10) at the mRNA level was determined by quantitative real-time polymerase chain reaction (qPCR) analysis. In newborn (day 1) rats, the increased HAAO expression in the depression group was significantly suppressed in the D+S group. It was observed that sertraline application increased IL6 expression compared to C and C+S groups. Expression levels in other genes were not changed. At the day of 30, the expression of KMO ve TNFα gene expression was increased in the depression group. The expression of the anti-inflammatory TGFβ gene was decreased in depression group. An increase in TGFβ and IL10 expression levels was observed with sertraline administration. In adult (day 150) rats, the increased expression of KMO, HAO and IL6 in the depression group was suppressed by sertraline administration. Findings showed that maternal depression alters the expression of kynurenine and cytokine genes. These results support its relationship with the psychopathological condition that the offspring may experience in the future.