Giorgetti, Elisa, Panesar, Moh, Zhang, Yunyu, Joller, Stefanie, Ronco, Marie, Obrecht, Michael, Lambert, Christian, Accart Gris, Nathalie, Beckmann, Nicolau, Doelemeyer, Arno, Perrot, Ludovic, Fruh, Isabelle, Mueller, Matthias, Pierrel, Eliane, Summermatter, Serge, Bidinosti, Michael, Shimshek, Derya, Lemire, Sophie and Nash, Mark (2019) Modulation of Microglia by Voluntary Exercise or CSF1R Inhibition Prevents Age-Related Loss of Functional Motor Units. Cell Reports, 29 (6). 1539-1554.e7. ISSN 22111247

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.

Item Type:	Article
Keywords:	aging CSF1R inhibition exercise innervation microglia motor unit neuroinflammation neuromuscular junction neuromuscular system spinal cord
Date Deposited:	11 Dec 2019 00:45
Last Modified:	11 Dec 2019 00:45
URI:	https://oak.novartis.com/id/eprint/41230