Isolation rearing impaired sensorimotor gating but increased pro-inflammatory cytokines and disrupted metabolic parameters in both sexes of rats

Social isolation rearing (SIR) is an early stress paradigm of deprivation of the social contact since weaning. SIR has been used to investigate the mechanisms behind certain mental illnesses with neurodevelopmental origins, including schizophrenia. In schizophrenia, metabolic dysfunction has become a critical issue with increasing evidence for a possible connection between metabolism and immune systems in which metabolic changes are associated with pro-inflammatory cytokine (pro-CK) levels. The present study employed a rat model of SIR with both sexes to examine behaviors [locomotor activity and prepulse inhibition (PPI)], inflammatory markers [C-reactive protein, interleukin (IL)-1 beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and interferon-gamma], and metabolism-related variables (body weight, blood pressure, and the profiles of glycemia and lipid). Our results revealed that around puberty, SIR rats of both sexes exhibited behaviorally a higher locomotor activity and a lower PPI performance. Biochemically, SIR rats had an elevated level of pro-CKs (IL-1 beta, IL-6, TNF-alpha, and interferon-gamma), and metabolic abnormalities (increased insulin resistance, decreased insulin sensitivity, and high blood pressure) in a time-dependent manner. The relationships between pro-CKs and metabolism were sex specific as IL-1 beta and interferon-gamma were correlated to glycemia metabolic indexes in males. The present study demonstrated SIR-induced longitudinal concomitant changes of pro-CKs and metabolic abnormalities, implying a more direct role of these two things in mental dysfunctions with a developmental origin.