Electron Microscopic Analysis of Myelin Thickness and Oligodendrocytes in Autism

Saturday, May 14, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
T. A. Avino1 and C. M. Schumann2, (1)University of California at Davis MIND Institute, Sacramento, CA, (2)UC Davis MIND Institute, Sacramento, CA
Background:   Structural and functional brain imaging studies support the prevailing hypothesis that autism involves disruptions to cortical network connectivity. Specifically, diffusion tensor imaging (DTI) studies of white matter in autism have reported reductions to the integrity of fiber tracts throughout the cerebrum and combined functional imaging studies demonstrate reduced cortical synchrony among brain areas. One potential explanation for this deficient communication in autism is alterations to the myelin sheathing these axons, which has been reported in the frontal lobe (Zikopoulos & Barbas, 2010). In the present study, we further examine these ultrastructural changes to the myelination of axons within the temporal lobe white matter in autism and explore the characteristics of oligodendrocytes from the same subjects as a potential mediator of these abnormal myelin findings. Our results have implications for the observed physiological disruptions in the disorder as well as informing how these ultrastructural changes may occur.

Objectives:   The goal of the present study was to assess the degree of myelination of axons occupying the temporal lobe white matter in individuals with autism relative to their age-matched typically developing counterparts. Furthermore, we examine these myelin thickness findings with regard to oligodendrocyte characteristics, such as their overall number, in the same subjects. 

Methods:   Data regarding the overall number of oligodendrocytes were acquired stereologically using an optical fractionator method from the amygdala in frozen 50μm sections of the temporal lobe (Morgan et al., 2015). From adjacent 50μm sections, white matter dissections were made from the superior temporal gyrus and fusiform gyrus within 4mm of the gray-white matter boundary and prepared for electron microscopic processing. Myelinated axons of varying sizes were randomly selected for myelin thickness measures (g-ratio) and imaged at 8,400x magnification. 

Results:   For all subjects, data from the g-ratio measures indicates proportionally thinner myelin with increasing axon diameter, which is consistent with previous reports. However, individuals with autism demonstrate thinner myelin in both cortical regions and across all axon sizes compared to their age-matched typically developing counterparts. Furthermore, these results show an age x diagnosis interaction wherein ASD subjects regress towards thinner myelin with increasing age whereas the typically developing subjects show a slow and gradual thickening of myelin with age. Lastly, correlation analysis reveals a strong positive relationship between the number of oligodendrocytes and myelin thickness in both ASD and typically developing subjects (r = .85, p < .01).

Conclusions:   Our data demonstrate a reduction of myelin thickness in autism affecting at least 2 cortical locations across all axon size classes potentially providing a substrate for which altered cortical communication and/or increased diffusivity is occurring in the disorder. These data are consistent with similar reports of alterations to myelinated axons in areas of the frontal lobe in autism (Zikopolous & Barbas, 2010) and also demonstrate abnormal myelination patterns with increasing age in autism. Our data also show a strong relationship between the number of oligodendrocytes and myelin thickness in both subject groups, potentially providing a mechanism for which hypomyelination and/or altered myelinated axon density is occurring in autism.