| First Author | Rangasamy SB | Year | 2023 |
| Journal | Brain Behav Immun | Volume | 109 |
| Pages | 204-218 | PubMed ID | 36682514 |
| Mgi Jnum | J:352196 | Mgi Id | MGI:7433951 |
| Doi | 10.1016/j.bbi.2023.01.009 | Citation | Rangasamy SB, et al. (2023) Treadmill workout activates PPARalpha in the hippocampus to upregulate ADAM10, decrease plaques and improve cognitive functions in 5XFAD mouse model of Alzheimer's disease. Brain Behav Immun 109:204-218 |
| abstractText | Although liver is rich in peroxisome proliferator-activated receptor alpha (PPARalpha), recently we have described the presence of PPARalpha 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 PPARalpha 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 PPARalpha 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(DeltaPPARalpha) mice (5XFAD mice lacking PPARalpha). On the other hand, treadmill workout increased ADAM10, decreased plaque pathology and protected memory and learning in 5XFAD(DeltaPPARbeta) mice (5XFAD mice lacking PPARbeta). Moreover, the other PPAR (PPARgamma) also did not play any role in the transcription of ADAM10 in vivo in the hippocampus of treadmill exercised 5XFAD mice. These results underline an important role of PPARalpha in which treadmill exercise remains unable to exhibit neuroprotection in the hippocampus in the absence of PPARalpha. |
