PI3K/Akt/NF-κB signaling pathway regulates behaviors in adolescent female rats following with neonatal maternal deprivation and chronic mild stress

The early-life aversive experiences are associated with the increased risk for adolescent neuropsychiatric disorders and neuroinflammation. So, we used neonatal maternal deprivation (NMD) and chronic mild stress (CMS) to build adolescent depression model and investigate the role of microglia activation, PI3K/Akt/NF-κB pathway in female rats. Pups in NMD group were separated from mothers for 3 h each day from postnatal day (PND) 2 to PND 21 and rats in CMS group were subjected to one mild stressor each day from PND 22 to PND 42. Sucrose preference test (SPT), open field test (OFT), novel objective recognition test (NORT), Elevated-plus maze (EPM), marble burying test (MBT) and forced swimming test (FST) were performed from PND 42 to PND 50. Iba-1, pPI3K/PI3K, pAkt/Akt, and NF-κB expressions in the prefrontal cortex (PFC) and hippocampus (HIP) were detected by Western-Blot. Contents of IL-6, IL-1β and TNF-α were detected by ELISA method. It was found NMD + CMS increased the immobility time, buried marble number, inflammatory cytokines release and reduced the sucrose consumption ratio, time ratio and distance ratio in open arm, crossing times, rearing times. Furthermore, it decreased the discrimination ratio (DR) and discrimination index (DI) in T2 phase. NMD + CMS upregulated the expression of Iba-1, pPI3K/PI3K, pacts/Akt, and NF-κB in PFC and HIP. NMD or CMS solely didn't affect all these behaviors in rats. Sertraline treatment reversed these changes after NMD + CMS. In view of our findings we propose the NMD + CMS procedure as a potentially useful animal model to analyze developmental emotional behaviors and cognitive dysfunction in adolescent female rats, which may be related with microglial activation and PI3k/Akt/NF-κB pathway upregulation.