Investigating Hippocampal Lateralization: Effects of Nickel on Neurobiological, AchE Activity, and Neurobehavioral Changes in the Wistar Rats.

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.