Modulation of Microglia by Voluntary Exercise or CSF1R Inhibition Prevents Age-Related Loss of Functional Motor Units

• DOI: 10.1016/j.celrep.2019.10.003
• Publication Date: 2019-11-05T15:58:49Z
• Authors: Elisa Giorgetti; Moh Panesar; Yunyu Zhang; Stefanie Joller; Marie Ronco; Michael Obrecht; Christian Lambert; Nathalie Accart; Nicolau Beckmann; Arno Doelemeyer; Ludovic Perrot; Isabelle Fruh; Matthias Mueller; Eliane Pierrel; Serge Summermatter; Michael Bidinosti; Derya R. Shimshek; Sophie Brachat; Mark Nash
• Keywords: Pathogenesis; Loss function

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 number units (MUs) can be maintained counteracting neurotoxic microglia in aged spinal cord. We observe marked changes, detected unit estimation (MUNE), occur prior mice. This coincides with gene expression changes indicative neuronal remodeling microglial activation Voluntary exercise prevents MUs reverses activation. Depleting CSF1R inhibition also age-related decline MUNE junction disruption, implying causal link. Our results suggest cord contribute mice demonstrate removal prevent or reverse MU loss.