Effects of glycoprotein synthesis inhibitor on myelination in rat cerebellum

Effects of a glycoprotein synthesis inhibitor on myelination were investigated in rat cerebellum. The glycoprotein synthesis inhibitor, tunicamycin (TM), was injected intracranially into newborn rats. The activity of 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) in the cerebellum was significantly reduced in 2-week-old animals and was restored to the normal level by age 3 weeks. When TM was injected into newborn rats every 3–4 days for a total of 6 times, CNPase activity was still low at 3 and 4 weeks. Immunohistochemical stainings for CNPase and myelin-associated glycoprotein (MAG) were performed on paraffin sections of multiple-TM-injected cerebellum at 3 weeks. The intensity of the staining with MAG antiserum in the white matter was clearly decreased in TM-treated cerebellum compared with the control. The myelin in the granule cell layer was poorly stained with CNPase antiserum in TM-treated cerebellum. Subcellular fractionation was carried out and the CNPase activity in each fraction was measured. The CNPase activity in the myelin fraction (P₂A) from the TM-treated cerebellum was significantly lower than that in the control. In contrast, the activity in the synaptosomal (P₂B) and microsomal (P₃) fractions from the multiple-TM-injected cerebellum was higher than in those from the controls. Polyacrylamide gel electrophoretic patterns of the P₂A fractions were analyzed. The P₂A fraction from TM-treated cerebellum contained less Wolfgram protein than the control. These results suggest that glycoprotein synthesis plays certain roles in myelination in the central nervous system.