title: Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic stripping.
abstract: Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic "synaptic stripping" was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions.
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Sajjan
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia; Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: R M D
authors.initials: RM
authors.lastname: Holsinger
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Fok
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ebrahimkhani
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: J L
authors.initials: JL
authors.lastname: Rollo
authors.affiliation: Discipline of Medical Radiation Sciences, Faculty of Health Sciences, The University of Sydney, Cumberland, NSW, Australia; Ramaciotti Imaging Center, Brain and Mind Research Institute, The University of Sydney, Camperdown, NSW, Australia; Australian Nuclear Science and Technology Organization, Lucas Heights, NSW, Australia.
authors.forename: R B
authors.initials: RB
authors.lastname: Banati
authors.affiliation: Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia. Electronic address: manuel@graeber.net.
authors.forename: M B
authors.initials: MB
authors.lastname: Graeber
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D020220:Facial Nerve Injuries / Q000503:physiopathology; D065828:Facial Nucleus / Q000502:physiology*; D042541:Intracellular Space / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D011917:Rats, Inbred Lew; D013569:Synapses / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D053508:Matrix Metalloproteinase 12; C000602031:matrix metallopeptidase 12, mouse; C000602030:matrix metallopeptidase 12, rat
keywords: extracellular matrix; facial nerve axotomy; matrikines; metzincins; statins; synaptic plasticity