Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat.
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.
Reddy
Gottipuolu R
GR
Department of Natural Sciences and Mathematics, Savannah State University, P.O. Box 20600, Savannah, GA 31404, USA.
Basha
Md Riyaz
MR
Devi
C Bhuvaneswari
CB
Suresh
Ambati
A
Baker
John L
JL
Shafeek
Abdul
A
Heinz
Josephine
J
Chetty
Chellu S
CS
D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000187:drug effects*; D000284:Administration, Oral; D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008431:Maternal-Fetal Exchange; D009474:Neurons / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D007854:Lead; D000110:Acetylcholinesterase