Immunohistochemical Investigations of the Thalamic Region in Rats Following Combined Exposure to Metals and Restraint Stress

Abstract

Chronic exposure to stress has been linked to the perturbation of normal brain functioning. Further, metal overexposure due to their increasing applications can negatively impact brain health. Combined exposure to stressful events and metals is common but has not yet been studied. Thus, this study focused on the thalamic region for its role as a vital relay station in the brain to investigate apoptotic and microglia activation, oxidative stress regulation, and myelin damage following co-exposures to restraint stress and metals, manganese (Mn) and nickel (Ni). Thirty-six adult male rats were divided into six groups and, respectively, exposed to the following for 15 days: control group (normal saline), stress group (3 hours of restraint stress daily), Mn and Ni only groups (intraperitoneal injection of 25 mg/kg of metals), and stress + metal groups received Mn or Ni prior to being subjected to restraint stress. Following treatments, immunohistochemical procedures were used to evaluate relevant neurochemical markers. Results show significantly increased activation of caspase-3 in stressed, metal-only, and combined stress-plus-metal treatments, particularly with Mn treatments. Also, the results show a varying response to Iba1, the microglia activation marker. Furthermore, the study reports significant decreases in Nrf2 (nuclear factor erythroid 2-related factor 2) expression that is potentiated by combined stress and metal treatments as well as altered myelination-linked proteins, Olig2 (oligodendrocyte lineage transcription factor 2), and MBP (myelin basic protein). Overall, the result from this study indicates that the combination of stress and metal exposure could exacerbate the neurotoxic impact of metal toxicity or stressful events.