Visual abnormalities associated with enhanced optic nerve myelination

Minzhong Yu, Subhadra Priyadarshini Narayanan, Feng Wang, Emily Morse, Wendy B. MacKlin, Neal S. Peachey

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Expression of the constitutively active serine/threonine kinase Akt in oligodendrocytes results in enhanced myelination in the CNS. Here, we have examined the effects of this Akt overexpression on optic nerve structure and on optic nerve function, assessed using the visual evoked potential (VEP). Transgenic mice have been generated with the Plp promoter driving expression of a modified form of Akt, in which aspartic acids are substituted for Thr308 and Ser473. These Plp-Akt-DD (Akt-DD) mice, and littermate controls, were studied at different ages. Optic nerves were examined anatomically at 2 and 6 months of age. At 2 months of age, optic nerves were substantially thicker in Akt-DD mice, reflecting an increase in myelination of optic nerve axons. By electron microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops, and the density of nodes of Ranvier was reduced, relative to control mice. We recorded VEPs in response to strobe flash ganzfeld stimuli presented after overnight dark- and light-adapted conditions at ages ranging from 1 to 10 months. It was possible to record a clear VEP from Akt-DD mice at all ages examined. At 1 month of age, VEP implicit times were somewhat shorter in Akt-DD transgenic mice than in control animals. Beyond 6 months of age, VEP latencies were consistently delayed in Akt-DD transgenic mice. These abnormalities did not reflect an alteration in retinal function as there were no significant differences between ERGs obtained from control or Akt-DD transgenic mice. In young mice, the somewhat faster responses may reflect improved transmission due to increased myelination of optic nerve axons. In older mice, where the Akt-DD optic nerve is markedly thicker than control, it is remarkable that optic nerves continue to function.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalBrain Research
Volume1374
DOIs
StatePublished - Feb 16 2011

Fingerprint

Optic Nerve
Visual Evoked Potentials
Transgenic Mice
Axons
Ranvier's Nodes
Protein-Serine-Threonine Kinases
Oligodendroglia
Myelin Sheath
Aspartic Acid
Electron Microscopy
Light

Keywords

  • Akt
  • Electroretinography
  • Myelination
  • Optic nerve
  • Visual evoked potential

ASJC Scopus subject areas

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

Cite this

Yu, M., Narayanan, S. P., Wang, F., Morse, E., MacKlin, W. B., & Peachey, N. S. (2011). Visual abnormalities associated with enhanced optic nerve myelination. Brain Research, 1374, 36-42. https://doi.org/10.1016/j.brainres.2010.12.043

Visual abnormalities associated with enhanced optic nerve myelination. / Yu, Minzhong; Narayanan, Subhadra Priyadarshini; Wang, Feng; Morse, Emily; MacKlin, Wendy B.; Peachey, Neal S.

In: Brain Research, Vol. 1374, 16.02.2011, p. 36-42.

Research output: Contribution to journalArticle

Yu, M, Narayanan, SP, Wang, F, Morse, E, MacKlin, WB & Peachey, NS 2011, 'Visual abnormalities associated with enhanced optic nerve myelination', Brain Research, vol. 1374, pp. 36-42. https://doi.org/10.1016/j.brainres.2010.12.043
Yu M, Narayanan SP, Wang F, Morse E, MacKlin WB, Peachey NS. Visual abnormalities associated with enhanced optic nerve myelination. Brain Research. 2011 Feb 16;1374:36-42. https://doi.org/10.1016/j.brainres.2010.12.043
Yu, Minzhong ; Narayanan, Subhadra Priyadarshini ; Wang, Feng ; Morse, Emily ; MacKlin, Wendy B. ; Peachey, Neal S. / Visual abnormalities associated with enhanced optic nerve myelination. In: Brain Research. 2011 ; Vol. 1374. pp. 36-42.
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