| First Author | Taha HB | Year | 2024 |
| Journal | Geroscience | PubMed ID | 39269584 |
| Mgi Jnum | J:360160 | Mgi Id | MGI:7787183 |
| Doi | 10.1007/s11357-024-01345-3 | Citation | Taha HB, et al. (2024) Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer's disease mouse model via enhancing neurotrophic and synaptic signaling. Geroscience |
| abstractText | Skeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle-originating factors ("myokines") with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimer's disease (AD) remain poorly understood. To investigate muscle-to-brain axis signaling in response to amyloid beta (Abeta)-induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages. Skeletal muscle TFEB overexpression reduced Abeta plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8-month-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP). Our findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD. |
