Hippocampal Growth Factor and Myokine Cathepsin B Expression following Aerobic and Resistance Training in 3xTg-AD Mice

Aerobic training (AT) can support brain health in Alzheimer's disease (AD); however, the role of resistance training (RT) in AD is not well established. Aside from direct effects on the brain, exercise may also regulate brain function through secretion of muscle-derived myokines. Aims. This study examined the effects of AT and RT on hippocampal BDNF and IGF-1 signaling, β-amyloid expression, and myokine cathepsin B in the triple transgenic (3xTg-AD) model of AD. 3xTg-AD mice were assigned to one of the following groups: sedentary (Tg), aerobic trained (Tg+AT, 9 wks treadmill running), or resistance trained (Tg+RT, 9 wks weighted ladder climbing) (n = 10/group). Rotarod latency and strength were assessed pre- and posttraining. Hippocampus and skeletal muscle were collected after training and analyzed by high-resolution respirometry, ELISA, and immunoblotting. Tg+RT showed greater grip strength than Tg and Tg+AT at posttraining (p < 0.01). Only Tg+AT improved rotarod peak latency (p < 0.01). Hippocampal IGF-1 concentration was ~15% greater in Tg+AT and Tg+RT compared to Tg (p < 0.05); however, downstream signals of p-IGF-1R, p-Akt, p-MAPK, and p-GSK3β were not altered. Cathepsin B, hippocampal p-CREB and BDNF, and hippocampal mitochondrial respiration were not affected by AT or RT. β-Amyloid was ~30% lower in Tg+RT compared to Tg (p < 0.05). This data suggests that regular resistance training reduces β-amyloid in the hippocampus concurrent with increased concentrations of IGF-1. Both types of training offered distinct benefits, either by improving physical function or by modifying signals in the hippocampus. Therefore, inclusion of both training modalities may address central defects, as well as peripheral comorbidities in AD.