Dynamics of chondroitin sulfation in the rat brain during development and vestibular compensation

Abstract

Chondroitin sulfate (CS) regulates neuronal plasticity by restricting neurite growth and synapse formation. Sulfation on C- 2 of glucuronic acid, C-4 and/ or C-6 of N-acetylgalactosamine of the repeating disaccharide units contributes to the heterogeneity and functions of CS. However, the regulation of CS sulfation in the brain is still poorly understood. We hypothesized that the abundance of different sulfated CS moieties changes in coordination with plastic changes in the brain. With fluorophore-assisted carbohydrate electrophoresis, we found that in both the cortex and the brainstem during postnatal development, mono-4-sulfated chondroitin moiety increased while mono-6-sulfated moiety decreased progressively to an undetectable level in adults. Di-2, 4 and 2, 6-sulfated moieties were not detectable in early postnatal stages but small amount could be found at later stages. We set forth to find changes in CS moieties in a plastic event in adult rat. Following unilateral labyrinthectomy in adult rats, we observed immediate deficits in posture, motor and ocular functions. Time taken for functional recovery reflected compensatory rewiring of the brainstem network. During the recovery period, expression of the mono-6-sulfated chondroitin moiety resumed, reminiscent of that in the early postnatal period. Real time PCR also revealed differences in the expression of chondroitin sulfotransferases between the left and right vestibular nucleus during early stage of vestibular compensation. Taken together, the developmental changes in CS sulfation and the rise of mono-6-sulfated moiety during vestibular compensation suggest a role of CS sulfation pattern in neuronal plasticity.