Journal of Depression and Anxiety
Open Access
ISSN: 2167-1044
ISSN: 2167-1044
Fredrick Otieno Oginga*, Thabisile Mpofana
Background: The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors Early Life Stress (ELS) and Parental Schizophrenia (PSZ) to affect immune system development, which in turn can impact brain development and its long-term functioning.
Objective: The present study aimed to explore the complex multifaceted interactions between early-life stress, Schizophrenia (SZ), and neuro-inflammation, and their collective effect on social interaction, locomotor function and spatial memory.
Methods: Male and female Sprague-Dawley rat pups were randomly assigned to eight groups: Control, ELS, schizophrenia, and ELS+schizophrenia. ELS was induced by Gestational Stress (GS) and Maternal Separation (MS) during the first two weeks of life, while SZ was induced by subcutaneous administration of ketamine. To assess behavioral changes, social interaction tests and sucrose preference tests were conducted. In addition, Neuro-inflammation was determined through DNA methylation, complete blood cell count and furthermore, we used ELISA kits to measure the expression levels of Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), and Interferon-gamma (IFN-g).
Results and conclusion: Our results revealed that both differential ELS and PSZ had a significant impairment in social interaction, social preference and spatial memory on the experimental groups compared to the control group (p<0.05). In addition, there was a decreased intersection of GFAP astrocyte processes in the hippocampus and Prefrontal Cortex (PFC) (p<0.01) and alterations in DNA methylation patterns. Furthermore, differential reductions were observed in the Neutrophil-to-Lymphocyte Ratio (NLR) (p<0.05), Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), and Interferon-gamma (IFN-g) were altered (p<0.05), indicating an inflammatory response. Gaining insights into the neuro-inflammatory pathways that contribute to motor and cognitive impairments could offer new therapeutic avenues for addressing the multifaceted challenges associated with this disorder.
Published Date: 2025-01-25; Received Date: 2023-09-10