Early Social Isolation Induces Anxiety- and Depression-Like Behaviors and Neuroinflammatory Responses in Rats

Exposure to stress during early developmental stages adversely affects brain development and is associated with psychiatric conditions such as depression and anxiety. In this study, we investigated behavioral changes and levels of oxidative stress and inflammatory mediators in the prefrontal cortex (PFC) of young male Wistar rats subjected to 6 weeks of chronic social isolation.Eighteen male Wistar Albino rats were divided into control and social isolation groups. The isolation group was housed individually for six weeks. Depressive- and anxiety-like behaviors were evaluated by the open field test (OFT) and forced swimming test (FST), respectively. Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), glycogen synthase kinase 3 beta (GSK-3β), brain derived neurotrophic factor (BDNF), malondialdehyde (MDA), and reduced glutathione (GSH) levels in the prefrontal cortex were measured. Group differences were analyzed using the Mann–Whitney U test.In the social isolation group, time spent in the center zone during the OFT was reduced, while time in the periphery was significantly increased compared to controls, indicating elevated anxiety-like behavior. Socially isolated rats also exhibited greater immobility in the FST, reflecting depression-like behavior, and showed elevated levels of TLR4, NF-κB, GSK-3β, and MDA. No statistically significant differences were observed between the groups in BDNF and GSH levels.Behavioral disturbances induced by early-life social isolation stress may involve increased oxidative stress in the PFC and activation of the NF-κB/TLR4/GSK-3β signaling pathway.