Integrity of White Matter is Compromised in Mice with Hyaluronan Deficiency.

Integrity of White Matter is Compromised in Mice with Hyaluronan Deficiency. Neurochem Res. 2019 Jun 07;: Authors: Sherpa AD, Guilfoyle DN, Naik AA, Isakovic J, Irie F, Yamaguchi Y, Hrabe J, Aoki C, Hrabetova S Abstract Brain white matter is the means of efficient signal propagation in brain and its dysfunction is associated with many neurological disorders. We studied the effect of hyaluronan deficiency on the integrity of myelin in murine corpus callosum. Conditional knockout mice lacking the hyaluronan synthase 2 were compared with control mice. Ultrastructural analysis by electron microscopy revealed a higher proportion of myelin lamellae intruding into axons of knockout mice, along with significantly slimmer axons (excluding myelin sheath thickness), lower g-ratios, and frequent loosening of the myelin wrappings, even though the myelin thickness was similar across the genotypes. Analysis of extracellular diffusion of a small marker molecule tetramethylammonium (74 MW) in brain slices prepared from corpus callosum showed that the extracellular space volume increased significantly in the knockout animals. Despite this vastly enlarged volume, extracellular diffusion rates were significantly reduced, indicating that the compromised myelin wrappings expose more complex geometric structure than the healthy ones. This finding was confirmed in vivo by diffusion-weighted magnetic resonance imaging. Magnetic resonance spectroscopy sugges...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research