Ca2+/calmodulin-mediated neurotransmitter release and neurobehavioural deficits following lead exposure.
The present study was designed to investigate the effect of in vitro and in vivo lead exposure on calmodulin-mediated neurotransmitter release from synaptic vesicles with a view to explain the mechanism involved in its behavioural effects. It was observed that lead stimulated calmodulin, in terms of its ability to activate cAMP phosphodiesterase, following in vitro and in vivo exposure. Lead was also seen to enhance calmodulin-mediated synaptic vesicle protein phosphorylation. The increase in lead-induced synaptic vesicle protein phosphorylation was accompanied by enhanced release of acetylcholine from synaptic vesicles following in vitro lead exposure by a calmodulin-dependent mechanism. The ability of Ca(2+)/calmodulin to evoke acetylcholine release was reduced in the synaptic vesicles isolated from lead-exposed animals. Concomitantly, the levels of acetylcholine were found to decrease by 37.8% in the lead-treated animals as compared to the controls. The neurochemical alterations following lead exposure were accompanied by neurobehavioural deficits in terms of impaired motor and cognitive functions. The results from the present study clearly suggest that lead exerts its neurotoxic effects by interfering with Ca(2+)/calmodulin-mediated neurotransmitter release that is eventually responsible for behavioural impairment.
Gill
K D
KD
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Panjab University, Chandigarh 160012, India.
Gupta
Vandana
V
Sandhir
Rajat
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D007854:Lead / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D002147:Calmodulin; D018377:Neurotransmitter Agents; D007854:Lead; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D000109:Acetylcholine; D002118:Calcium