Developmental lead neurotoxicity: Alterations in brain cholinergic system

Abstract

Developing brain has been shown to be susceptible to the neurotoxic effects of lead (Pb). Our earlier studies (Reddy GR, Riyaz Basha Md, Devi CB, Suresh A, Baker JL, Shafeek A, Heinz J, Chetty CS. Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat. Int J Devl Neurosci 2003;21:347–52) have shown decrease in acetylcholinesterase (AChE) activity in the crude homogenates of cerebellum and hippocampus of rat brain exposed to Pb. In this study, we have further examined in detail, the alterations in AChE activity and acetylcholine (ACh) levels in different brain regions using histochemical and spectrophotometric methods. Rats were lactationally exposed to low level (0.2%) and high level (1%) Pb. The studies were conducted in young (1 month) and adult (3 months) rats. Pb exposure significantly decreased the specific activity of AChE and increased the levels of ACh in the synaptosomal fractions of cerebellum, hippocampus and cerebral cortex in a dose- and age-dependent manner. These alterations in AChE and ACh were more predominant in young rat brain as compared to adult brain. Maximum AChE activity and ACh level as well as maximum alterations following Pb exposure were observed in synaptosomes of hippocampus. Histochemical studies also showed higher AChE activity in the hippocampal region compared to other areas of brain as revealed by the intensity of AChE staining. Though high level Pb exposure remarkably decreased the intensity of AChE staining in the dentate gyrus, CA2 and CA3 areas of hippocampus, and different cell layers of cortex and cerebellum, highly significant loss of AChE activity was observed in the CA3 region of hippocampus, molecular layer of cerebellum and cortical cell layers. These data suggest that Pb exposure may selectively affect cholinergic system in brain areas controlling learning and cognitive behavior.