The presence of enzymes, e.g., carbonic anhydrase (ca) and 5'-nucleotidase, in the myelin sheath has been substantiated by quantitative biochemical data and immunocytochemical localization. Most recently, investigations into the functions of these enzymes in myelin and glial cells were undertaken. In particular, the high specific activities of both acetyl-CoA carboxylase and ca in oligodendrocytes suggested a role for ca in the biosynthesis of myelin lipids. The availability of a carbonic-anhydrase-- deficient mutant mouse will now provide a unique opportunity to test more directly certain hypothetical functions of ca: e.g., the putative roles in the synthesis of myelin lipids and in compaction of the myelin sheath. Parameters that will be compared in the brains of mutant and control mice include myelin yields, ultrastructure of the myelin sheath and susceptibility to pentylenetetrazole seizures. A second series of experiments will be concerned with two isoenzymes of glutathione-S-transferase (GST) in the brain. Supporting data will be collected concerning one GST isoenzyme, Yp, as a myelin- (and oligodendrocyte-) associated enzyme in the mouse brain, and hypothetical roles of the GST's in detoxication and hormone action will be tested by examining the effects of glutathione depletion on the neurotoxicity of triethyltin and on glucocorticoid induction of glycerol-phosphate dehydrogenase in the brain. In a third series of experiments, studies will be initiated concerning expression of ca and GST's during remyelination after cuprizone intoxication and during reactive gliosis resulting from trimethyltin intoxication. Demyelination and gliosis often are consequences of neurotoxicity and the inflammatory response (e.g., in multiple sclerosis). Since ca and GST are multifunctional, it is expected that these enzymes will have important roles in the CNS, perturbation of which could trigger demyelination and/or gliosis and interfere with myelination or remyelination. In addition, the capabilities for remyelination in the CNS and susceptibility to gliosis will depend upon whether the genes for the glial-cell enzymes can be transcribed and translated after the early stages of development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012890-16
Application #
2262488
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1979-01-01
Project End
1997-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
16
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Cammer, W B; Brion, L P (2000) Carbonic anhydrase in the nervous system. EXS :475-89
Tansey, F A; Cammer, W (1998) Differential uptake of dextran beads by astrocytes, macrophages and oligodendrocytes in mixed glial-cell cultures from brains of neonatal rats. Neurosci Lett 248:159-62
Cammer, W (1998) Glial-cell cultures from brains of carbonic anhydrase II-deficient mutant mice: delay in oligodendrocyte maturation. Neurochem Res 23:407-12
Tansey, F A; Zhang, H; Cammer, W (1997) Rapid upregulation of the Pi isoform of glutathione-S-transferase in mouse brains after withdrawal of the neurotoxicant, cuprizone. Mol Chem Neuropathol 31:161-70
Brion, L P; Cammer, W; Satlin, L M et al. (1997) Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice. Am J Physiol 273:F234-45
Cammer, W; Zhang, H (1996) A reexamination of ganglioside GD3-immunopositive glial cells in the forebrains of rats and mice less than 1 week of age. J Histochem Cytochem 44:143-9
Tansey, F A; Zhang, H; Cammer, W (1996) Expression of carbonic anhydrase II mRNA and protein in oligodendrocytes during toxic demyelination in the young adult mouse. Neurochem Res 21:411-6
Cammer, W; Zhang, H (1996) Carbonic anhydrase II in microglia in forebrains of neonatal rats. J Neuroimmunol 67:131-6
Cammer, W; Zhang, H (1996) Ganglioside GD3 in radial glia and astrocytes in situ in brains of young and adult mice. J Neurosci Res 46:18-23
Cammer, W; Zhang, H; Tansey, F A (1995) Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse. J Neurosci Res 40:451-7

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