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Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat
Gottipuolu R Reddy1, Md Riyaz Basha, C Bhuvaneswari Devi
1Department of Natural Sciences and Mathematics, Savannah State University, P.O. Box 20600, Savannah, GA 31404, USA.
Insights
Perinatal lead (Pb) exposure alters brain development, reducing acetylcholinesterase (AChE) activity in the hippocampus and cerebellum. These changes persist after lead withdrawal, potentially causing cognitive and behavioral deficits.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Neurochemistry
Background:
- Early childhood lead (Pb) exposure is linked to behavioral and cognitive impairments.
- The developing brain, particularly the hippocampus and cerebellum, is highly vulnerable to neurotoxicants.
Purpose of the Study:
- To investigate the effects of perinatal lead exposure on acetylcholinesterase (AChE) activity in the developing rat hippocampus and cerebellum.
- To assess the long-term consequences of lead exposure on cholinergic system function and behavior.
Main Methods:
- Pregnant rats received 0.2% lead acetate from gestation day 6 to postnatal day 21.
- Acetylcholinesterase (AChE) activity was measured in hippocampus and cerebellum at various time points up to 5 weeks.
- Histochemical analysis and in vitro studies were performed to evaluate AChE activity and lead's inhibitory effects.
- Open-field behavioral tests were conducted.
Main Results:
- Lead exposure significantly decreased AChE activity in both brain regions, with effects increasing with age.
- Histochemistry revealed reduced AChE in specific hippocampal and cerebellar layers.
- In vitro studies showed lead inhibited AChE in a concentration-dependent manner, with potentiation by eserine at low lead concentrations.
- Behavioral tests indicated decreased activity in lead-exposed and eserine-treated rats.
Conclusions:
- Low-level perinatal lead exposure induces lasting alterations in the cholinergic system of the developing brain.
- These neurochemical changes in the hippocampus and cerebellum may underlie observed behavioral and learning deficits.
- The findings highlight the persistent neurotoxic effects of early-life lead exposure.
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.
