CHOLINERGIC DENERVATION-LIKE CHANGES IN RAT HIPPOCAMPUS FOLLOWING DEVELOPMENTAL LEAD-EXPOSURE

We investigated the effects of developmental lead exposure from embryo nic day 16 (E16) through postnatal day 28 (PN28), on cholinergic and c atecholaminergic markers in the septohippocampal pathway in rats throu gh fourth month of age. Lead exposure resulted in a persistent 30-40% reduction of [H-3]hemicholinium-3 ([H-3]HC-3) binding in the hippocamp us through PN120, and 20-30% reduction of septal and hippocampal choli ne acetyltransferase (ChAT) activity which persisted through PN84 but returned to control levels in both septum and hippocampus at PN112. Th e muscarinic ligand [H-3]quinuclidinyl benzylate ([H-3]QNB) binding wa s reduced in the septum at PN28 but did not differ significantly from controls at PN56-PN112. Neither short- nor long-term effects of Pb exp osure on [H-3]QNB binding were seen in the hippocampus. Similar to the effects of fimbria-fornix transection, Pb exposure resulted in a long -term 50-90% increase of tyrosine hydroxylase(TH) activity in the hipp ocampus, although neither treatment affected TH activity in the septum . The lead-induced increase in hippocampal TH was significantly attenu ated by superior cervical ganglionectomy. It is concluded that the eff ects of perinatal lead exposure resemble in several respects those see n following surgical disruption of the septohippocampal pathway in adu lt animals. The denervation-like effects in the hippocampus may be an important factor in long-term learning and cognitive impairments follo wing developmental exposure to low-levels of lead.