Dose-Dependent Effects of Lead Acetate on Cerebral Cortex Cytoarchitecture and Cholinergic–Gabaergic Neurotransmission in Adult Male Wistar Rats

Abstract

Background: Lead (Pb) remains one of the most pervasive environmental neurotoxicants worldwide, and the developing and adult central nervous system is particularly vulnerable to its dose-dependent effects. Although the cholinergic and oxidative consequences of lead exposure have been documented, the combined histopathological and neurochemical (acetylcholine, acetylcholinesterase, and γ-aminobutyric acid [GABA]) consequences of graded oral lead acetate exposure on the adult cerebral cortex remain incompletely characterised. Methods: Twenty adult male Wistar rats (150–200 g) were randomly allocated into four groups (n = 5/group): a distilled-water control, and three groups administered lead acetate at 100, 200, and 400 mg/kg body weight by oral gavage daily for 21 days. Serum acetylcholine, acetylcholinesterase (AChE) activity, and GABA concentration were measured, and cerebral cortical sections were processed for haematoxylin and eosin (H&E) histology. Data were analysed by one-way ANOVA followed by Duncan's Multiple Range Test (p < 0.05). Results: Lead acetate produced a dose-dependent increase in serum acetylcholine (from ~730 pg/mL in controls to ~970 pg/mL at 400 mg/kg) accompanied by a dose-dependent decline in AChE activity (from ~22 IU/L to ~14.8 IU/L) and GABA concentration (from ~7.1 to ~4.6 µmol/mL), all significant at p < 0.05 relative to control. Histologically, the control cortex showed normal neuropil with ramified, resting microglia and quiescent astrocytes, whereas lead-exposed cortices showed progressive, dose-related microglial activation, astrogliosis, and neuropil vacuolation, culminating in severe neuropil disorganisation and amoeboid microglial transformation at 400 mg/kg. Conclusion: Subacute oral lead acetate exposure produces concurrent, dose-dependent cholinergic dysregulation, GABAergic suppression, and neuroinflammatory histopathology in the adult rat cerebral cortex, supporting a multi-mechanistic model of lead neurotoxicity in which impaired acetylcholine catabolism, loss of inhibitory tone, and glial activation act in concert to compromise cortical integrity.