Fig. 12
The lack of MHCI signaling anticipated the onset of disease but increase the overall survival of mSOD1 mice. Schematic representation of (a) hindlimb and (b) forelimb motor unit of SOD1G93AB2m+/+ (G93A +/+) and SOD1G93AB2m−/− (G93A−/−) mice at early and late disease stages. a The interaction of MHCI and CTLs in the PNS is essential to preserve the quality of the connections of motor axons with rapidly degenerating hindlimb muscles, independently from MN loss. This could explain the earlier motor onset in G93A−/− mice. These animals, while partially preserving MNs (due the lack of MHCI-mediated interaction of microglia and CTLs), are not able to activate the neuroprotective stress MHCI signalling in the PNS. This lead to an earlier denervation atrophy of hindlimb muscles. b In the cervical nerves, the extent of stress is not such as to cause an activation of MHCI signalling in the PNS of G93A+/+ mice. As a consequence, the denervation atrophy of forelimbs is mainly dependent on the health status of the MN cell body in the cervical spinal cord. In G93A−/− mice, the lack of MHCI-mediated interaction of microglia and CTLs results in lower inflammation and higher protection of MNs. Accordingly, the greater functionality of forelimbs causes these mice survive more than G93A+/+ mice