Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne factors.Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and neurogenesis.Methods:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-β and treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise.For in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP) were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a) plasma from the exercise-trained rats,(b) plasma from sedentary rats,or(c) saline.Cognitive function,amyloid plaque pathology,and neurogenesis were assessed.The plasma used for the treatment was analyzed for 23 cytokines.Results:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032) and reduced atrophy by 50.0%(p <0.001) in amyloid-β-treated cells.In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by ～3 fold,regardless of pathological stage,when compared to saline-treated rats.Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma.Conclusion:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain.This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.