Evaluating the Dose-Dependent Impact of Lead Acetate on Hippocampal Structure and Cholinergic Neurotransmission in Adult Male Wistar Rats

Abstract

Background: Lead (Pb) is a pervasive environmental neurotoxicant with well-documented deleterious effects on the central nervous system. Despite decades of research, the dose-response relationship governing hippocampal structural integrity and cholinergic neurotransmission following subacute oral lead acetate exposure remains incompletely characterized. Objective: This study investigated the dose-dependent effects of oral lead acetate administration on brain and body weight, hippocampal histoarchitecture, and acetylcholine levels in adult male Wistar rats over a 21-day exposure period. Methods: Twenty adult male Wistar rats (150–200 g) were randomly assigned to four groups (n = 5 each): a control group receiving distilled water, and three treatment groups receiving lead acetate at doses of 100, 200, and 400 mg/kg body weight per day via oral gavage. Animals were sacrificed at the end of the experiment; brain and body weights were recorded, hippocampal sections were processed for haematoxylin and eosin (H&E) staining, and acetylcholine levels were quantified. Results: Lead acetate administration produced dose-dependent reductions in body weight, with the highest dose (400 mg/kg) causing a 6.43% reduction from baseline. Brain weight showed limited variation across groups (1.58–1.79 g). Histological examination revealed progressive hippocampal degeneration characterized by pyramidal cell layer disorganization, reduced neuronal density, pyknotic nuclei, and extensive neuropil vacuolation, most pronounced in the 400 mg/kg group. Acetylcholine levels increased significantly across treatment groups in a dose-dependent manner (p < 0.05). Conclusion: Subacute oral lead acetate exposure induces dose-dependent neurotoxic effects in the rat hippocampus, with marked structural degeneration and cholinergic perturbation. These findings provide experimental evidence for the neurodegeneration-promoting capacity of lead and highlight the hippocampal cholinergic system as a sensitive target of lead neurotoxicity.