Reduction of choline acetyltransferase mRNA in the septum of developing rat exposed to inorganic lead.

We previously reported that perinatal exposure to low levels of lead (Pb) results in a pronounced reduction of choline acetyltransferase (ChAT) activity in the septohippocampal pathway of the rat. In the present study we employed a ChAT specific 43-base oligonucleotide hybridization probe to compare the developmental expression of ChAT mRNA and ChAT activity in the septum of normal and Pb-exposed rats. Rats were exposed to Pb via maternal administration of 0.2% solution of Pb acetate in drinking water from one week before birth through postnatal day 21 (PN21). In normal animals, the developmental changes in the ChAT mRNA and activity levels were temporally correlated and approached adult levels by PN21. In the Pb-exposed pups, ChAT mRNA and activity levels were reduced respectively by 69% and 50% at PN7, 47% and 33% at PN14, and 47% and 22% at PN21. In contrast, Pb exposure had no significant effect on either ChAT mRNA or ChAT activity in the dams. These results indicate that cholinotoxicity of Pb in the septohippocampal pathway of the rat involves developmental stage-dependent disruption of ChAT gene expression.