{"title":"Subchronic effects of HgCl<sub>2</sub> on cognitive function and central inflammation in type 2 diabetic rats: involvement of BDNF and acetylcholinesterase.","authors":"Douae Benloughmari, Samir Bikri, Meriam El Aboubi, Fatima-Zahra Yassif, Youssef Aboussaleh","doi":"10.3389/ftox.2025.1610720","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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<sub>2</sub>), 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.</p><p><strong>Aim: </strong>This study aimed to evaluate the subchronic effects of HgCl<sub>2</sub> on cognitive performance and neuroinflammation in a rat model of T2DM, with a particular focus on the roles of BDNF and acetylcholinesterase (AChE).</p><p><strong>Materials and methods: </strong>The experimental design included four groups: control, HgCl<sub>2</sub>-treated, diabetic, and diabetic rats treated with HgCl<sub>2</sub>. T2DM was induced by intraperitoneal injections of streptozotocin (STZ) and nicotinamide (NA). Rats in the HgCl<sub>2</sub>-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.</p><p><strong>Results: </strong>The findings revealed a significant increase in fasting blood glucose levels in both diabetic and HgCl<sub>2</sub>-treated diabetic groups compared to controls (P < 0.001). Moreover, HgCl<sub>2</sub> 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).</p><p><strong>Conclusion: </strong>Overall, these results highlight the synergistic impact of hyperglycemia and HgCl<sub>2</sub> exposure in exacerbating neuroinflammation and cognitive decline, suggesting a critical interaction between metabolic and environmental neurotoxic factors.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1610720"},"PeriodicalIF":4.6000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301335/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/ftox.2025.1610720","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
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Abstract
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 (HgCl2), 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 HgCl2 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, HgCl2-treated, diabetic, and diabetic rats treated with HgCl2. T2DM was induced by intraperitoneal injections of streptozotocin (STZ) and nicotinamide (NA). Rats in the HgCl2-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 HgCl2-treated diabetic groups compared to controls (P < 0.001). Moreover, HgCl2 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 HgCl2 exposure in exacerbating neuroinflammation and cognitive decline, suggesting a critical interaction between metabolic and environmental neurotoxic factors.
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