Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat

Abstract

Exposure to low-levels of lead (Pb) during early development has been implicated in behavioral abnormalities and cognitive deficits in children. The present study is focused on developmental changes in hippocampus and cerebellum of rats following perinatal exposure to Pb. Pregnant rats were exposed to 0.2% Pb-acetate from gestation day 6 (GD 6) through postnatal day (PND) 21 and the activity levels of acetylcholinesterase (AChE) were estimated in cerebellum and hippocampus of pups at specific time points for 5 weeks. In both the brain regions, Pb-exposure decreased AChE activity with an increase in age. Histochemical observations conducted in 35 days old rat brain showed decreased AChE activity conspicuously in stratum oriens and dentate gyrus of hippocampus, and molecular and granule cell layers of cerebellum. In vitro studies conducted in 35 days old rat brain showed a considerable decrease in the specific activity of AChE at high concentrations (50-100 microM) of Pb in a concentration-dependent manner. However, at low concentrations (5-20 microM), Pb failed to produce such changes. In the presence of eserine (physostigmine), the specific inhibitor of AChE, the inhibitory effect of Pb was potentiated and this was more pronounced at low-concentrations of Pb. The behavioral responses in open-field also showed a significant decrease in both Pb exposed as well as eserine administered rats. These data suggest that low-level perinatal Pb-exposure induces alterations in cholinergic system in the cerebellum and hippocampus of developing brain even after the withdrawal of Pb-exposure, that may contribute to behavioral and learning deficits.

Neurobehavioral changes in mice offspring induced by prenatal exposure to acute toxicity of sodium selenite

“…Acetylcholine can be a marker in teratological studies (Ajarem & Ahmad 1991, 1998, since any change in the behavior process due to any toxicant is indicated by alteration in acetylcholine (Reddy et al 2003). It was found that selenite suppressed the acetylcholine at PD7 and at PD14.…”

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

“…Experimental studies have shown that during development, the cholinergic system is especially sensitive to environmental insults (e.g., ethanol, lead, organophosphates, tobacco smoke; Eriksson et al, 2001;Reddy et al, 2003;Robinson, 2002;Thomas et al, 2000). These and other insults would certainly have the potential to interact with genetic vulnerabilities affecting brain development to produce deficits which could contribute to disease states.…”

Zinc and Calcium Reduce Lead Induced Perturbations in the Aminergic System of Developing Brain

“…Pb-induced effects on the dopaminergic system include changes in the synthesis, turnover and reuptake of dopamine, changes in the levels of dopamine and its metabolites, as well as changes in the number of dopamine receptors (Cory-Slechta 1995). Inspite of several publications addressing the action of Pb on neurotransmitter systems and the associated enzymes such as acetylcholinesterase (AChE), MAO and nitric oxide synthase (NOS) (Govoni et al 1979;Reddy et al 2002Reddy et al , 2003, it is often difficult to compare these studies because reports are highly variable and many observations lack confirmation by other laboratories.…”