Subchronic effects of HgCl(2) on cognitive function and central inflammation in type 2 diabetic rats: involvement of BDNF and acetylcholinesterase.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major global health concern frequently related with chronic low-grade inflammation and a spectrum of cognitive impairments, including deficits in learning and memory. Mercury chloride (HgCl(2)), a widespread environmental pollutant, is recognized for its neurotoxic properties and its capacity to trigger inflammatory responses, particularly in patients with metabolic disorders such as T2DM. AIM: This study aimed to evaluate the subchronic effects of HgCl(2) on cognitive performance and neuroinflammation in a rat model of T2DM, with a particular focus on the roles of BDNF and acetylcholinesterase (AChE). MATERIALS AND METHODS: The experimental design included four groups: control, HgCl(2)-treated, diabetic, and diabetic rats treated with HgCl(2). T2DM was induced by intraperitoneal injections of streptozotocin (STZ) and nicotinamide (NA). Rats in the HgCl(2)-exposed groups received an oral dose of 0.375 mg/kg/day for 45 consecutive days. Cognitive performance was assessed using behavioral tests targeting spatial learning, recognition memory, and working memory. Additionally, hippocampal and prefrontal cortex (PFC) levels of TNF-α, IL-6, BDNF, and AChE activity were measured to evaluate neuroinflammatory and neurotoxic responses. RESULTS: The findings revealed a significant increase in fasting blood glucose levels in both diabetic and HgCl(2)-treated diabetic groups compared to controls (P < 0.001). Moreover, HgCl(2) administration in diabetic rats led to a more pronounced impairment in cognitive functions compared to untreated diabetic rats (P < 0.05). These deficits were associated with enhanced neuroinflammatory markers (TNF-α and IL-6), decreased AChE activity, and reduced BDNF expression in the PFC and hippocampus (P < 0.05). CONCLUSION: Overall, these results highlight the synergistic impact of hyperglycemia and HgCl(2) exposure in exacerbating neuroinflammation and cognitive decline, suggesting a critical interaction between metabolic and environmental neurotoxic factors.