The pathologic role for COX-2 in apoptotic oligodendrocytes in virus induced demyelinating disease: implications for multiple sclerosis.
The objective of this study was examine whether the inducible isoform of the enzyme cyclooxygenase (COX-2) was expressed in dying oligodendrocytes in the Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating disease (TMEV-IDD), an experimental animal model for multiple sclerosis (MS). COX-2 is an enzyme that is tightly coupled to neuronal excitotoxic death. Since neuronal expression of COX-2 contributes to the susceptibility of neurons to excitotoxic death, we asked whether COX-2 was expressed in oligodendrocytes in MS plaques and in lesions during TMEV-IDD. COX-2 was expressed in oligodendrocytes in chronic active lesions from two MS patients. Similar pathology was present in TMEV-IDD spinal cord lesions. COX-2 was expressed in oligodendrocytes four weeks after infection with TMEV coincident with the onset of demyelination. A marker for apoptotic death, activated caspase 3, was present in a subset of oligodendrocytes that expressed COX-2. Oligodendrocyte expression of COX-2 in TMEV-IDD and MS lesions is consistent with a pathological role for this enzyme in demyelination. The presence of the cell death marker (activated caspase 3) with COX-2 in oligodendrocytes is direct evidence linking COX-2 with cell death of oligodendrocytes in these demyelinating diseases.
Carlson
Noel G
NG
Geriatric Research Education and Clinical Center (GRECC), Salt Lake City, UT 84148, USA. noel.carlson@med.va.gov
Hill
Kenneth E
KE
Tsunoda
Ikuo
I
Fujinami
Robert S
RS
Rose
John W
JW
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D039481:CD11b Antigen / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007239:Infections; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism*; D009836:Oligodendroglia / Q000201:enzymology*; D011509:Proteoglycans / Q000378:metabolism; D017945:Theilovirus / Q000472:pathogenicity; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D039481:CD11b Antigen; D053148:Caspase 3; D020169:Caspases; D051546:Cyclooxygenase 2; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C505409:Casp3 protein, mouse