Figure 3.

Age-related decline in mean cortical cholinergic innervation is reversed by NGF gene delivery to cholinergic somata in the basal forebrain. AChE staining in the insular cortex of young, aged-control, and aged-NGF-grafted rhesus monkeys. (A) The normal density of cholinergic axons is illustrated in young subjects. (B) Axon density is reduced in aged-control grafted subjects. (C) AChE-stained fiber density is increased significantly in aged monkeys that received grafts of autologous NGF-secreting fibroblasts into Ch4i. (A–C, scale bar = 35 μm.) (D) Quantification of cholinergic axon density. To compare cholinergic innervation densities across multiple cortical regions, normalized z scores of density measurements from each cortical region were calculated and then averaged. A significant overall group effect was present by one-way ANOVA (P < 0.0001). Aging was associated with a significant reduction in overall cholinergic fiber density (*, P < 0.0001, post hoc Fisher's lsd), which was restored in recipients of NGF-secreting cells. Black bars, young monkeys; red bars, aged controls; blue bars, aged NGF-grafted subjects. Error bars represent SEM.