1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced astrogliosis does not require activation of ornithine decarboxylase.
Mechanical injury to the brain results in enhanced immunostaining for glial fibrillary acidic protein (GFAP) that is markedly inhibited by difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. In the current study, systemic exposure of mice to the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), also increased GFAP but, unlike mechanical injury, this increase was not prevented by DFMO pretreatment. These results indicate that de novo polyamine biosynthesis is not obligatory for the MPTP-induced increase in GFAP. MPTP administration, unlike mechanical injury, does not disrupt the blood-brain barrier; thus, a role for polyamine biosynthesis in the astrocyte response to injury may be restricted to insults involving a compromised blood-brain barrier.
O'Callaghan
J P
JP
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Seidler
F J
FJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism*; D005911:Gliosis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020267:MPTP Poisoning; D051379:Mice; D008810:Mice, Inbred C57BL; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D012016:Reference Values
D005904:Glial Fibrillary Acidic Protein; D009955:Ornithine Decarboxylase; D000518:Eflornithine