Biochemical changes in Cuprizone-induced spongiform encephalopathy. I. Changes in the activities of 2',3'-cyclic nucleotide 3'-phosphohydrolase, oligodendroglial ceramide galactosyl transferase, and the hydrolysis of the alkenyl group of alkenyl, acyl-glycerophospholipids by plasmalogenase in different regions of the brain.
Cuprizone (biscyclohexanone oxaldihydrazone) which is known to produce a status spongiosus and demyelination in the CNS was administered in the diet of weanling male mice at a concentration of 0.4% by weight for a period of six weeks before returning animals to a normal diet. Changes in body weight but not brain weight were reversible. Based on the decline in CNP'ase activity and the concentration of galactocerebroside, the loss of myelin was around 70% in those sections of the cerebrum with a high content of white matter while the cerebellum was less affected. The activity of oligodendroglial HFA-ceramide galactosyl transferase was also reduced. These biochemical parameters of myelination were increased after withdrawal of Cuprizone. Remyelination in the cerebrum but not the cerebellum was incomplete. The activity of plasmalogenase hydrolysing the alkenyl group of alkenyl, acyl-phospholipids increased 2-fold in those sections in which myelin loss was most severe. The increase preceded the greatest loss of myelin components (3 to 6 weeks on Cuprizone). The origin of the increased phospholipase activity in demyelinating tissue is discussed. Following myelination, there was a deficit in plasmalogenase activity particularly in the frontal cortex of the cerebrum, where the plasmalogen concentration was higher than in controls.
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003471:Cuprizone; D003510:Cyclohexanes; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000201:enzymology*; D038983:Galactolipids; D005700:Galactosyltransferases / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism*; D008297:Male; D051379:Mice; D051146:N-Acylsphingosine Galactosyltransferase; D009836:Oligodendroglia / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism
D003510:Cyclohexanes; D038983:Galactolipids; D006017:Glycolipids; D010955:Plasmalogens; C020791:phosphatidal ethanolamines; D003471:Cuprizone; D005700:Galactosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase; D006867:Hydrolases; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse; C022403:plasmalogenase