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Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Soleman, Sara 
Tumbarello, David A  ORCID logo  https://orcid.org/0000-0002-5169-0561
Mason, Matthew RJ 

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.

Description

Keywords

adeno-associated virus, axon initial segment, dorsal root ganglia, integrin, retinal ganglion cell, sensorimotor cortex, Animals, Animals, Newborn, Axons, Brain, Ganglia, Spinal, Genetic Vectors, Integrin alpha Chains, Integrin alpha6, Integrin beta1, Male, Optic Nerve, Rats, Inbred Lew, Rats, Sprague-Dawley, Sciatic Nerve, Spinal Cord, Spinal Cord Injuries

Journal Title

eNeuro

Conference Name

Journal ISSN

2373-2822
2373-2822

Volume Title

3

Publisher

Society for Neuroscience
Sponsorship
Medical Research Council (G1000864)
MRC (G1000864)
Medical Research Council (G0701518)
Henry Smith Charity (20093773)