The effects of long-term voluntary exercise on the morphology and function of the septo-hippocampal cholinergic system in aged rats

Abstract

The aim of the present study was to analyze the effects of long-term voluntary exercise on the septo-hippocampal cholinergic system in aged rats. We examined neuronal morphology (number and size of choline acetyltransferase [ChAT]-positive cells in the medial septum) and function (extracellular acetylcholine [ACh] release and regional blood flow responses in the hippocampus [Hpc BF] during treadmill walking). Aged male F344 rats were housed individually in sedentary cages (control group) or in cages with a running wheel (exercise group) for 5–6 months, and then used for experiments at the age of 27–28 months. The results revealed that while the number of ChAT-positive cells in the exercise groupwas similar to that in the control group, themean size of the ChAT-positive cells was larger in the exercise group than in the control group. The magnitude of the walking-induced increase in the extracellular level of ACh in the hippocampus in the exercise group was similar to that observed in the control group. However, the magnitude of the walkinginduced increase in Hpc BF was higher in the exercise group than in the control group. Mecamylamine, a nicotinic receptor (nAChR) antagonist, produced a more pronounced reduction in the magnitude of the Hpc BF response in the exercise group than in the control group. Thus, the differences in the magnitude of the Hpc BF response between the two groups disappeared after the administration of mecamylamine. These results suggest that repeated activation of the septo-hippocampal cholinergic system by long-term voluntary exercise prevents age-related atrophy of the cholinergic neurons, while enhancing hippocampal cholinergic vasodilation as a result of increased ACh sensitivity of the nAChRs. (The Autonomic Nervous System, 44: 29–36, 2007)