Abstract
Purpose: :
Constitutive expression of the serine/threonine kinase Akt in oligodendrocytes results in enhanced myelination in the CNS. Here, we have examined the effects of this process on optic nerve function, assessed using the visual evoked potential (VEP), and optic nerve structure.
Methods: :
Transgenic mice express a modified form of Akt, in which aspartic acids are substituted for Thr308 and Ser473 under the control of the Plp promoter (Flores et al., J Neurosci 2008;28:7174). These Akt-DD mice, and littermate controls, were studied at ages ranging from 1 to 10 months. We recorded VEPs and electroretinograms (ERGs) in response to strobe flash ganzfeld stimuli presented after overnight dark adaptation and under light-adapted conditions. Optic nerves were examined at 6 months of age with respect to axon diameter and myelination.
Results: :
There were no significant differences in ERGs obtained from control or Akt-DD transgenic mice. 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. At 2 months of age, optic nerves were substantially thicker in Akt-DD mice, reflecting an increase in myelination for each optic nerve axon. At that age, by electron microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops. However, there was no change in axon number or diameter in Akt-DD transgenic mice. The density of nodes of Ranvier was reduced, relative to control mice.
Conclusions: :
VEP studies provide a measure of transmission through the Akt-DD optic nerve. 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.
Keywords: electrophysiology: non-clinical • electroretinography: non-clinical • neuro-ophthalmology: optic nerve