El Brouzi Mohamed Yassine, Lamtai Mouloud, Bousalham Rim, Zghari Oussama, Abouyaala Oumaima, Baghdad Wissal, Fath Nada, Hamzaoui Abdelghafour El, Rezqaoui Ayoub, Otmani Rida El, Touil Tarik, Hessni Aboubaker El, Mesfioui Abdelhalem
Laboratory of Biology and Health, Neuro-Immunology and Behaviour Unit, Faculty of Science, Ibn Tofail University, NeurosciencesKenitra, Morocco.
Department of Neurophysiology, Mohammed V Military Instruction Hospital, Rabat, Morocco.
Mol Neurobiol. 2025 Aug 5. doi: 10.1007/s12035-025-05251-3.
Nickel (Ni) is a heavy metal that is widely distributed in the environment and has harmful effects on human health, especially the central nervous system. Ni's accumulation capacity makes the hippocampus, a crucial brain region for memory and cognitive functions, particularly sensitive to its effects. However, the mechanisms underlying Ni neurotoxicity in the hippocampus are poorly understood. Our study aims to explore the neurotoxic effects of Ni on the hippocampus, highlighting differences between the right and left hippocampus in male Wistar rats. Using an integrated approach, we investigated the affective and cognitive changes. In addition, we assessed markers of cytotoxicity (LDH), cholinergic neurotransmission (AchE), neuroinflammation (Complement (C3 and C4), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6) and Interleukin 1beta (IL-1β)), and oxidative stress (Nitric oxide (NO), Thiobarbituric acid reactive substances (TBARS), Catalase (CAT), Superoxide dismutase (SOD), and Glutathione (GSH) in right and left hippocampal homogenate) following intrahippocampal Ni injection. Neurobehavioral tests revealed significant alterations in the affective and cognitive functions of Ni-exposed rats in the hippocampus. In addition, analysis of hippocampal lateralization revealed differences in the effects of Ni between the right and left hippocampus. Ni administration into the hippocampus induced cytotoxicity and a significant decrease in AchE activity. Markers of neuroinflammation were also detected, with increased levels of complement compounds and proinflammatory cytokines. Furthermore, an increase in oxidative stress markers was observed. Finally, histological analyses revealed structural and cytotoxic changes in the hippocampus, confirming the harmful effects of Ni exposure. This study provides valuable insight into the mechanisms underlying Ni neurotoxicity, and underlines for the first time, the importance of taking hippocampal lateralization into account in neurotoxicology studies.
镍（Ni）是一种重金属，广泛分布于环境中，对人体健康，尤其是中枢神经系统具有有害影响。镍的蓄积能力使海马体（对记忆和认知功能至关重要的脑区）对其影响尤为敏感。然而，镍在海马体中产生神经毒性的潜在机制尚不清楚。我们的研究旨在探讨镍对海马体的神经毒性作用，突出雄性Wistar大鼠左右海马体之间的差异。我们采用综合方法研究了情感和认知变化。此外，我们评估了细胞毒性标志物（乳酸脱氢酶）、胆碱能神经传递标志物（乙酰胆碱酯酶）、神经炎症标志物（补体（C3和C4）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和白细胞介素1β（IL-1β））以及海马体内注射镍后左右海马体匀浆中的氧化应激标志物（一氧化氮（NO）、硫代巴比妥酸反应性物质（TBARS）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH））。神经行为测试显示，镍暴露大鼠海马体的情感和认知功能发生了显著改变。此外，海马体侧化分析显示，镍对左右海马体的影响存在差异。向海马体注射镍会诱导细胞毒性，并导致乙酰胆碱酯酶活性显著降低。还检测到了神经炎症标志物，补体化合物和促炎细胞因子水平升高。此外，观察到氧化应激标志物增加。最后，组织学分析揭示了海马体的结构和细胞毒性变化，证实了镍暴露的有害影响。本研究为镍神经毒性的潜在机制提供了有价值的见解，并首次强调了在神经毒理学研究中考虑海马体侧化的重要性。
