Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged rhesus monkey.

Quantitative studies were conducted to determine the number and size of cholinergic neurons in the medial septal nucleus of four aged (23-25 years old) and four young (10-12 years old) rhesus monkeys. All of the animals had been tested on an extensive battery of learning and memory tasks prior to these experiments. Two of the aged monkeys displayed a pattern of recognition memory deficits that resembled the effects of medial temporal lobe damage. The postmortem anatomical data were analyzed in relation to both the age and behavioral status of the animals. Across all rostrocaudal levels of the medial septal nucleus, there was a 19.3% decrease in the number of cholinergic neurons in the aged monkeys. The loss was regionally selective, however, and ranged from a low of 6.2% rostrally to 40.9% caudally. The degree of cell loss was similar in both memory-impaired and memory-unimpaired aged animals. Morphological analysis also revealed that the mean cross-sectional area of cholinergic neurons was significantly larger in the aged animals. At caudal levels, the increase in average cell size was at least partly due to a disproportionate loss of small to medium size neurons. At rostral levels of the medial septal nucleus, however, where there was minimal cell loss, a clear hypertrophy of cholinergic neurons was evident. Interestingly, the cell hypertrophy observed at these rostral levels was present only in brains from the behaviorally impaired aged monkeys. These findings represent the first morphological demonstration of alterations in cholinergic neurons in the aged nonhuman primate.(ABSTRACT TRUNCATED AT 250 WORDS)