Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity

Hannah J. Hoehn, Yvonne Kress, Albert Sohn, Celia F. Brosnan, Sarah Bourdon, Bridget Shafit-Zagardo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Activation of the receptor tyrosine kinase Axl recruits signaling molecules that regulate cell growth and survival. To evaluate Axl's role in brain during cuprizone toxicity, mice were fed cuprizone and evaluated at 3-, 4-, and 6-week cuprizone treatment and 3- and 5-week post-cuprizone withdrawal. At 4-week cuprizone treatment, the corpora callosa of wildtype (WT) mice had robust Oil Red O+ staining indicative of ongoing phagocytosis. Axl-/- mice had minimal Oil Red O+ staining, fewer microglia, and significantly more TUNEL+/ASPA+ mature oligodendrocytes than the WT. At 6-week cuprizone treatment, there was significantly more Oil Red O+ staining in the Axl-/- corpora callosa than in the WT indicating a lag in the clearance of cellular and myelin debris. Relative to WT mice, there were fewer mature oligodendrocytes and significantly more SMI-32+ axons at 3-week post-cuprizone withdrawal, indicative of axonal damage in the Axl-/- corpora callosa. Electron microscopy determined that at 3-week post-cuprizone withdrawal the number of dystrophic axons and axons containing autophagosome-like vacuoles/mouse was increased in the Axl-/- mice relative to the WT mice. In Axl-/- corpora callosa, 5-week post-cuprizone withdrawal, the number of mature oligodendrocytes was comparable to the WT mice, but axons in the Axl-/- mice were SMI-32+, suggesting that Axl-/- mice have delayed clearance of apoptotic oligodendrocytes and myelin debris resulting in prolonged axonal damage and recovery from cuprizone toxicity.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Volume1240
DOIs
StatePublished - Nov 13 2008

Fingerprint

Cuprizone
Corpus Callosum
Oligodendroglia
Axons
Staining and Labeling
Myelin Sheath
In Situ Nick-End Labeling
Microglia
Vacuoles
Phagocytosis
Cell Survival
Electron Microscopy

Keywords

  • Autophagy
  • Axonal damage
  • Copper toxin
  • Myelination
  • Oligodendrocyte maturation
  • Phagocytosis
  • Vesicle

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity. / Hoehn, Hannah J.; Kress, Yvonne; Sohn, Albert; Brosnan, Celia F.; Bourdon, Sarah; Shafit-Zagardo, Bridget.

In: Brain Research, Vol. 1240, 13.11.2008, p. 1-11.

Research output: Contribution to journalArticle

Hoehn, Hannah J. ; Kress, Yvonne ; Sohn, Albert ; Brosnan, Celia F. ; Bourdon, Sarah ; Shafit-Zagardo, Bridget. / Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity. In: Brain Research. 2008 ; Vol. 1240. pp. 1-11.
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