Cholinergic denervation-like changes in rat hippocampus following developmental lead exposure.

We investigated the effects of developmental lead exposure from embryonic day 16 (E16) through postnatal day 28 (PN28), on cholinergic and catecholaminergic markers in the septohippocampal pathway in rats through fourth month of age. Lead exposure resulted in a persistent 30-40% reduction of [3H]hemicholinium-3 ([3H]HC-3) binding in the hippocampus through PN120, and 20-30% reduction of septal and hippocampal choline acetyltransferase (ChAT) activity which persisted through PN84 but returned to control levels in both septum and hippocampus at PN112. The muscarinic ligand [3H]quinuclidinyl benzylate ([3H]QNB) binding was reduced in the septum at PN28 but did not differ significantly from controls at PN56-PN112. Neither short- nor long-term effects of Pb exposure on [3H]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 hippocampus, although neither treatment affected TH activity in the septum. The lead-induced increase in hippocampal TH was significantly attenuated by superior cervical ganglionectomy. It is concluded that the effects of perinatal lead exposure resemble in several respects those seen following surgical disruption of the septohippocampal pathway in adult animals. The denervation-like effects in the hippocampus may be an important factor in long-term learning and cognitive impairments following developmental exposure to low-levels of lead.