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Astrocyte-associated fibronectin is critical for axonal regeneration in adult white matter
Journal article   Open access   Peer reviewed

Astrocyte-associated fibronectin is critical for axonal regeneration in adult white matter

Veronica J Tom, Catherine M Doller, Alfred T Malouf and Jerry Silver
The Journal of neuroscience, v 24(42), pp 9282-9290
20 Oct 2004
PMID: 15496664
url
https://doi.org/10.1523/JNEUROSCI.2120-04.2004View
Published, Version of Record (VoR) Open

Abstract

Immunohistochemistry Neurons, Afferent - cytology Myelin Sheath - physiology Cell Proliferation Fibronectins - analysis Neurites - physiology Tissue Culture Techniques Nerve Regeneration - physiology Rats Mice, Transgenic Axons - physiology Ganglia, Spinal - cytology Cerebral Cortex - cytology Rats, Sprague-Dawley Laminin - analysis Corpus Callosum - cytology Astrocytes - physiology Animals Corpus Callosum - chemistry Aging - physiology Astrocytes - chemistry Fibronectins - physiology Mice
Although it has been suggested that astroglia guide pioneering axons during development, the cellular and molecular substrates that direct axon regeneration in adult white matter have not been elucidated. We show that although adult cortical neurons were only able to elaborate very short, highly branched, dendritic-like processes when seeded onto organotypic slice cultures of postnatal day 35 (P35) rat brain containing the corpus callosum, adult dorsal root ganglion (DRG) neurons were able to regenerate lengthy axons within the reactive glial environment of this degenerating white matter tract. The callosum in both P35 slices and adult rat brain was rich in fibronectin, but not laminin. Furthermore, the fibronectin was intimately associated with the intratract astrocytes. Blockade of fibronectin function in situ with an anti-fibronectin antibody dramatically decreased outgrowth of DRG neurites, suggesting that fibronectin plays an important role in axon regeneration in mature white matter. The critical interaction between regrowing axons and astroglial-associated fibronectin in white matter may be an additional factor to consider when trying to understand regeneration failure and devising strategies to promote regeneration.

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