Treadmill workout activates PPAR? in the hippocampus to upregulate ADAM10, decrease plaques and improve cognitive functions in 5XFAD mouse model of Alzheimer?s disease

Although liver is rich in peroxisome proliferator-activated receptor alpha (PPAR alpha), recently we have described the presence of PPAR alpha in hippocampus where it is involved in non-amyloidogenic metabolism of amyloid precursor protein (APP) via ADAM10, decreasing amyloid plaques and improving memory and learning. However, mechanisms to upregulate PPAR alpha in vivo in the hippocampus are poorly understood. Regular exercise has multiple beneficial effects on human health and here, we describe the importance of regular mild treadmill exercise in upregulating PPAR alpha in vivo in the hippocampus of 5XFAD mouse model of Alzheimer's disease. We also demonstrate that treadmill exercise remained unable to stimulate ADAM10, reduce plaque pathology and improve cognitive functions in 5XFAD Delta PPAR alpha mice (5XFAD mice lacking PPAR alpha). On the other hand, treadmill workout increased ADAM10, decreased plaque pathology and protected memory and learning in 5XFAD Delta PPAR beta mice (5XFAD mice lacking PPAR beta). Moreover, the other PPAR (PPAR gamma) also did not play any role in the tran-scription of ADAM10 in vivo in the hippocampus of treadmill exercised 5XFAD mice. These results underline an important role of PPAR alpha in which treadmill exercise remains unable to exhibit neuroprotection in the hippo -campus in the absence of PPAR alpha.