Developmental stage-dependent protective effect of NGF against lead cholinotoxicity in the rat septum

The ability of nerve growth factor (NGF) to ameliorate developmental cholinotoxicity of inorganic lead (Pb) for the septal neurons was investigated by making intracerebroventricular injections of single doses of 30 microg 2.5S NGF into maternally lead-exposed suckling rats on postnatal days P2, P4, P11, or P18. Administration of NGF on P4 or later induced septal choline acetyltransferase (ChAT) activity to the same relative extent in both Pb-exposed as in control rats but failed to reverse the net reductions of ChAT activity induced by Pb. In contrast, injection of NGF at P2 completely restored ChAT activity in Pb-exposed pups to control levels by preventing the loss of ChAT-immunoreactive cells in the septum. It is concluded that although NGF retains the capacity to upregulate ChAT throughout the period of Pb exposure, it protects against the Pb-induced loss of septal cholinergic neurons only when applied within the critical period of Pb-vulnerability between postnatal days 2 and 4.