Effect of intracerebroventricular infusion of NGF on the loss and recovery of the cholinergic phenotype. A, The septohippocampal path was axotomized and NGF-infusion was performed for two weeks. Left, quantification of septal cholinergic neurons in the lesioned side as compared to the contralateral side in untreated animals (control), lesioned animals (lesion) and lesioned animals brain-infused with NGF (lesion + NGF sim.). Right, light microscopy of anti-NGF immunohistochemistry showing the wide distribution of infused NGF and uptake of NGF by septal neurons. Exogenous NGF infused right after axotomy protects cholinergic cells from ChAT-loss. B, The septohippocampal path was axotomized and 3 weeks after the axotomy (delayed NGF-infusion), NGF was infused for two additional weeks. This procedure did not protect cholinergic cells from ChAT-loss, contrary to the protection observed with simultaneous infusion. C, Confocal microscopy of double immunofluorescence against TrkA and ChAT showing the colocalization of these markers in septal neurons 21 days after axotomy (inferior panel). There are no ChAT-negative cells positive for TrkA, suggesting that neurons cannot respond to NGF 3 weeks post-axotomy due to down-regulation of NGF receptors.