Benloughmari Douae, Bikri Samir, El Aboubi Meriam, Yassif Fatima-Zahra, Aboussaleh Youssef
Faculty of Sciences, Laboratory of Biology and Health, Ibn Tofail University, Kenitra, Morocco.
Higher School of Technology, Ibn Tofail University, Kenitra, Morocco.
Front Toxicol. 2025 Jul 14;7:1610720. doi: 10.3389/ftox.2025.1610720. eCollection 2025.
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), 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.
This study aimed to evaluate the subchronic effects of HgCl on cognitive performance and neuroinflammation in a rat model of T2DM, with a particular focus on the roles of BDNF and acetylcholinesterase (AChE).
The experimental design included four groups: control, HgCl-treated, diabetic, and diabetic rats treated with HgCl. T2DM was induced by intraperitoneal injections of streptozotocin (STZ) and nicotinamide (NA). Rats in the HgCl-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.
The findings revealed a significant increase in fasting blood glucose levels in both diabetic and HgCl-treated diabetic groups compared to controls (P < 0.001). Moreover, HgCl 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).
Overall, these results highlight the synergistic impact of hyperglycemia and HgCl exposure in exacerbating neuroinflammation and cognitive decline, suggesting a critical interaction between metabolic and environmental neurotoxic factors.
2型糖尿病（T2DM）是一个主要的全球健康问题，常与慢性低度炎症以及一系列认知障碍相关，包括学习和记忆缺陷。氯化汞（HgCl）是一种广泛存在的环境污染物，以其神经毒性特性及其引发炎症反应的能力而闻名，特别是在患有代谢紊乱如T2DM的患者中。
本研究旨在评估HgCl对T2DM大鼠模型认知表现和神经炎症的亚慢性影响，特别关注脑源性神经营养因子（BDNF）和乙酰胆碱酯酶（AChE）的作用。
实验设计包括四组：对照组、HgCl处理组、糖尿病组和HgCl处理的糖尿病大鼠组。通过腹腔注射链脲佐菌素（STZ）和烟酰胺（NA）诱导T2DM。HgCl暴露组的大鼠连续45天接受口服剂量0.375mg/kg/天。使用针对空间学习、识别记忆和工作记忆的行为测试评估认知表现。此外，测量海马和前额叶皮质（PFC）中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、BDNF水平以及AChE活性，以评估神经炎症和神经毒性反应。
研究结果显示，与对照组相比，糖尿病组和HgCl处理的糖尿病组的空腹血糖水平均显著升高（P<0.001）。此外，与未处理的糖尿病大鼠相比，给糖尿病大鼠施用HgCl导致认知功能损害更明显（P<0.05）。这些缺陷与神经炎症标志物（TNF-α和IL-6）增强、AChE活性降低以及PFC和海马中BDNF表达减少有关（P<0.05）。
总体而言，这些结果突出了高血糖和HgCl暴露在加剧神经炎症和认知衰退方面的协同作用，表明代谢和环境神经毒性因素之间存在关键相互作用。
