title: A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy.
abstract: Recently, MHC class I molecules have been shown to be important for the retraction of synaptic connections that normally occurs during development [Huh, G.S., Boulanger, L. M., Du, H., Riquelme, P. A., Brotz, T. M. & Shatz, C. J. (2000) Science 290, 2155-2158]. In the adult CNS, a classical response of neurons to axon lesion is the detachment of synapses from the cell body and dendrites. We have investigated whether MHC I molecules are involved also in this type of synaptic detachment by studying the synaptic input to sciatic motoneurons at 1 week after peripheral nerve transection in beta2-microglobulin or transporter associated with antigen processing 1-null mutant mice, in which cell surface MHC I expression is impaired. Surprisingly, lesioned motoneurons in mutant mice showed more extensive synaptic detachments than those in wild-type animals. This surplus removal of synapses was entirely directed toward inhibitory synapses assembled in clusters. In parallel, a significantly smaller population of motoneurons reinnervated the distal stump of the transected sciatic nerve in mutants. MHC I molecules, which traditionally have been linked with immunological mechanisms, are thus crucial for a selective maintenance of synapses during the synaptic removal process in neurons after lesion, and the lack of MHC I expression may impede the ability of neurons to regenerate axons.
authors.affiliation: Department of Neuroscience and Department of Microbiology, Tumor Biology Center, and Strategic Research Center IRIS, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Alexandre L R
authors.initials: AL
authors.lastname: Oliveira
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thams
authors.forename: Olle
authors.initials: O
authors.lastname: Lidman
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Hans
authors.initials: H
authors.lastname: Lindå
authors.forename: Staffan
authors.initials: S
authors.lastname: Cullheim
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D019771:Axotomy; D002470:Cell Survival; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D005810:Multigene Family / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D016708:Synaptophysin / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D016708:Synaptophysin; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin