AI Article Synopsis
- Age-related loss of motor neurons affects muscle function, but the exact cause is still not well understood.
- Research on mice shows that neurotoxic microglia in the spinal cord play a role in this decline, as changes in motor units occur before muscle function decreases.
- Voluntary exercise and depleting harmful microglia can prevent or reverse this decline, suggesting that targeting these microglia might help maintain muscle health in aging.
Article Abstract
Age-related loss of skeletal muscle innervation by motor neurons leads to impaired neuromuscular function and is a well-established clinical phenomenon. However, the underlying pathogenesis remains unclear. Studying mice, we find that the number of motor units (MUs) can be maintained by counteracting neurotoxic microglia in the aged spinal cord. We observe that marked innervation changes, detected by motor unit number estimation (MUNE), occur prior to loss of muscle function in aged mice. This coincides with gene expression changes indicative of neuronal remodeling and microglial activation in aged spinal cord. Voluntary exercise prevents loss of MUs and reverses microglia activation. Depleting microglia by CSF1R inhibition also prevents the age-related decline in MUNE and neuromuscular junction disruption, implying a causal link. Our results suggest that age-related changes in spinal cord microglia contribute to neuromuscular decline in aged mice and demonstrate that removal of aged neurotoxic microglia can prevent or reverse MU loss.
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| http://dx.doi.org/10.1016/j.celrep.2019.10.003 | DOI Listing |
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