Abstract

Background:
Lead (Pb) is a powerful heavy metal that was associated to various neurological diseases including saturnism. Previous studies have reported its marked neurotoxicity, involving several neurotransmitters systems and their related neurobehavioral functions.

Aim:
This study aims to investigate the neurotoxicological impacts of acute and chronic Pb exposure on the dopaminergic innervations and astroglia reactivity along with the subsequent locomotor outcomes.

Methods:
The acute model involved daily i.p. injections of Pb acetate (25 mg/kg B.W.) for three days, while chronic exposure was achieved by supplementing maternal drinking water with 0.3% Pb acetate over 82 days (gestation through lactation). Curcumin I was administered by oral gavage at a dose of 30 mg/kg B.W. in the acute model, and 16 mg/kg B.W. in the chronic one to assess its neuroprotective potential. Using immunohistochemistry, we monitored tyrosine hydroxylase (TH) levels within the SNpc and glial fibrillary acidic protein (GFAP) expression in the frontal cortex, while locomotor activity was assessed via the open-field test.

Results:
The results demonstrated that both acute and chronic exposures to Pb significantly increased cerebral Pb concentrations. Behaviorally, acute exposure induced locomotor hyperactivity contrarily to the chronic Pb exposure. At the cellular level, acute Pb exposure was associated with increased tyrosine hydroxylase (TH) immunoreactivity within the SNpc, while chronic Pb exposure elicited a significant decline in TH expression in the same region. Furthermore, GFAP immunoreactivity in the frontal cortex was elevated across both intoxication models. Notably, these neurochemical and behavioural alterations were significantly attenuated by curcumin administration, underscoring its neuroprotective potential against Pb-induced toxicity.

Conclusion:
Our findings demonstrated that Pb exposure alters the dopaminergic and astroglial systems, leading to significant locomotor disturbances. These impairments were significantly restored by Curcumin I, leading to consider this molecule as a potential natural neuroprotective agent against Pb-induced neurotoxicity.

Key words: Dopaminergic system; Intoxication; Lead; Neurotoxicity; Rat.