Neuroinflammation and microglial expression in brains of social-isolation rearing model of schizophrenia

Abstract

Schizophrenia is a psychiatric disorder with a global prevalence of approximately 0.45%. It is considered a mental illness, with negative symptoms, positive symptoms, and cognitive dysfunction. The outcomes of studies on the role of microglia and neuroinflammation have been conflicting. In addition, there is a poor understanding of the sex differences in microglial expression and neuroinflammation markers in the prefrontal cortex, hippocampus, and nucleus accumbens. Understanding the exact roles of neuroinflammation may guide the development of efficient therapeutic drugs that can address the negative, positive, and cognitive symptoms of the disease. We examined the effect of social isolation rearing on schizophrenia-related behaviours in male and female BALB/c mice. The social-isolation rearing protocol started on post-natal day (PND) 21, lasting for 35 days. Animals were assigned to four cohorts, consisting of five animals per group. On PND 56, animals were assessed for behavioural changes. We used enzyme-linked immunosorbent assays to investigate the expression of nuclear factor kappa B (NF-κB), tumour necrosis factor-α (TNF-α), and Interleukin-1β (IL-1β) in the hippocampus, nucleus accumbens, and prefrontal cortex. Immunohistochemistry was used to assess the expression of microglia in the three brain regions. Our study showed that isolation rearing led to increasing locomotion, heightened anxiety, depression, and a reduced percentage of prepulse inhibition. There was a significant increase (p < 0.05) in anxiety in the female isolation mice compared to male isolation mice. Furthermore, isolation rearing significantly increased microglia count (p < 0.05) in the hippocampus, nucleus accumbens, and prefrontal cortex, only in the male group. There was microglial hyper-activation as evident in the downregulation of CX3CR1 in both male and female social-isolation groups. Male social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers only in the nucleus accumbens while the female social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers in both the nucleus accumbens and hippocampus. The study showed that therapeutic interventions aimed at modulating CX3CR1 activity and reducing inflammation may be beneficial for patients with schizophrenia.