title: Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.
abstract: The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype.
authors: School of Medicine, University of St Andrews, North Haugh , St Andrews, KY16 9TF, United Kingdom.
authors: Melissa R
authors: 0000-0001-5960-5619
authors: MR
authors: Andrews
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge, CB2 0PY, United Kingdom.
authors: Sara
authors: S
authors: Soleman
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge, CB2 0PY, United Kingdom.
authors: Menghon
authors: 0000-0003-1659-3771
authors: M
authors: Cheah
authors: Biological Sciences, University of Southampton, Highfield Campus , Southampton, SO17 1BJ, United Kingdom.
authors: David A
authors: 0000-0002-5169-0561
authors: DA
authors: Tumbarello
authors: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, Meibergdreef 47, Amsterdam 1105BA, The Netherlands.
authors: Matthew R J
authors: MR
authors: Mason
authors: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, Meibergdreef 47, Amsterdam 1105BA, The Netherlands.
authors: Elizabeth
authors: 0000-0003-0746-5081
authors: E
authors: Moloney
authors: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, Meibergdreef 47, Amsterdam 1105BA, The Netherlands ; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognition research, Vrije Universiteit Amsterdam, Amsterdam 1081HV, The Netherlands.
authors: Joost
authors: J
authors: Verhaagen
authors: Neurodegenerative Disease Laboratory, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
authors: Jean-Charles
authors: JC
authors: Bensadoun
authors: Neurodegenerative Disease Laboratory, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
authors: Bernard
authors: 0000-0001-5485-8748
authors: B
authors: Schneider
authors: Neurodegenerative Disease Laboratory, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
authors: Patrick
authors: P
authors: Aebischer
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge, CB2 0PY, United Kingdom.
authors: James W
authors: JW
authors: Fawcett
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005822:Genetic Vectors; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009900:Optic Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D039001:Integrin alpha Chains; D039503:Integrin alpha6; D019012:Integrin beta1; C084613:integrin alpha9
keywords: adeno-associated virus; axon initial segment; dorsal root ganglia; integrin; retinal ganglion cell; sensorimotor cortex