Perinatal low-level lead exposure and the septo-hippocampal cholinergic system: selective reduction of muscarinic receptors and cholineacetyltransferase in the rat septum.

We investigated the effects of low-level lead exposure on the postnatal development of cholinergic muscarinic receptors (mAChR) and a cholinergic marker enzyme cholineacetyltransferase (ChAT) activity in the rat septum and hippocampus. Rat pups were maternally lead-exposed by giving 0.2% lead acetate in drinking water to dams from one week before parturition (gestational day 16) through weaning at postnatal day 28. The lead-exposed litters had blood Pb in the range 20 micrograms/dl and tissue Pb < 0.2 micrograms/g in both the septum and hippocampus. Associated with this level of lead exposure there was a significant 30-40% reduction in the ChAT activity in the septa and hippocampi of PN7 through PN28 animals. In contrast, the levels of glutamic acid decarboxylase (GAD) activity, a GABAergic neuron marker enzyme, were not altered in either brain region. Associated with the selective reduction of ChAT activity there was a parallel 30-40% reduction of the [3H]quinuclidinyl benzilate, [3H]AF-DX 384, and [3H]pirenzepine binding in the septum, however muscarinic ligand binding in the hippocampus of lead exposed animals was not affected. These results indicate preferential vulnerability of septal cholinergic neurons to adverse effects of low-level Pb exposure and suggest that impaired expression of muscarinic receptors and disruption of muscarinic transmission in the septum may be an important factor in cognitive and learning deficits associated with developmental low-level lead exposure.