Adhesion molecules and synapse remodeling during motoneuron regeneration

摘要: Spinal motoneurons integrate a vast synaptic input and are the final conveyors of motor commands to skeletal muscle. Motoneuron regeneration includes altered contacts between motoneuron several other cell types. The severed axon elongates along Schwann cells in nerve, while types glia interact closely with lesioned spinal cord. Simultaneously, disrupted when synapses lost from process called stripping. aim this thesis project was identify potential mediators interactions during regeneration, special emphasis on molecules that could be importance for remodeling. A reduced expression adhesion has been speculated involved stripping motoneurons. Over last years, such have described which influence formation maintenance synapses, also mediate events occur as guidance myelination. We demonstrate peripheral axotomy sciatic results molecules, many previously unstudied context. Some these changes indicate possible involvement synapse elimination, whereas may regenerative events. Specifically, nectin-1 -3 increased motoneurons, did nectin-3-binding necl-5. Nectin proteins not localize but instead neuronal processes glia, both within cord nerve. Immunoreactivity N-cadherin localized surface after nerve transection (SNT). mRNA encoding Ncadherin axotomy, immunoreactivity molecule Axotomy resulted SynCAM3/necl-1 SynCAM4/necl-4 indicates remyelination. SynCAM1/necl-2, SynCAM2/necl-3, neuroligin (NLG) -2 were expressed by unlesioned SynCAM bodies. In vitro synapse-inducing properties, following SNT, SynCAM1 NLG2 decreased rapidly, prior loss staining synaptophysin pool. correlated return SNT. NLG smaller degree crush than although similar lesion models. Finally, work ongoing, complement-tagging CNS removal demonstrated visual system. investigated whether complement axotomized Complement C3 mice displayed lesion, larger upregulation growth-associated protein 43 more rapid restoration function. conclude response involves downregulation molecules. Expression correlates magnitude NLGs does seem reflect synapses. Contact distal stump stimulate NLGs, SynCAM1. sole determinant elimination since pattern wild type mice. is required normal elimination. Thus, target therapeutic attempts preserve circuits.