Aging is associated with a diffuse impairment of forebrain cholinergic neurons

The study evaluates whether any degenerative changes affect forebrain cholinergic systems during natural aging. The medial septal nucleus, the nuclei of the diagonal band, the neostriatum, and the basal nucleus were studied in adult and aged Wistar rats. Butcher's technique for acetylcholinesterase allowed us to identify neurons located in these forebrain nuclei, which stained intensely or moderately for the enzyme and were putatively cholinergic. The size of forebrain regions containing stained neurons, and the number and size of stained perikarya located therein, were measured. In aged rats, the size of forebrain cholinergic nuclei was reduced by an average of 26%. The density of neurons located in these regions was also significantly lower in aged rats than in controls; intensely stained neurons displayed a mean reduction of 27.81%, while intensely and moderately stained perikarya together were reduced by 25.43%. Cross-sectional area of the stained perikarya was also reduced in aged rats by 32.87%. These data show that the number of forebrain acetylcholinesterase-containing neurons is reduced in aged rats. They are consistent with the hypothesis that natural aging brings about a diffuse and homogeneous depletion of forebrain cholinergic perikarya. Neurons which are viable, and can be selectively stained, show morphological alterations, which are likely to be related to a degenerative process.