The neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) increases glial fibrillary acidic protein and decreases dopamine levels of the mouse striatum: evidence for glial response to injury.
The neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), administered to male or female mice, decreased striatal dopamine content and increased the levels of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP). The rise in GFAP was evident as early as two days following the last dose of MPTP, was maximal 7 days after the toxicant and returned to control levels by two months, post MPTP. Striatal dopamine content was decreased post-MPTP administration, showing a slight recovery between one and two months after the toxicant. No differences were observed among male and female mice in their responses to the toxicant. Hippocampal noradrenaline content was not affected by the toxicant, neither was the GFAP content altered by MPTP in this structure. Additionally, pargyline pretreatment prevented both the rise in GFAP and the decrease in dopamine in striatum. MPTP produced a smaller elevation in GFAP levels within a midbrain section of tissue containing the substantia nigra, without significantly decreasing the dopamine content of this structure, suggesting neurotoxic involvement at the level of dopamine perikarya. The toxicant did not affect the molecular radius of the protein detected by the antibody to GFAP, as determined by immunoblot analysis.
Reinhard
J F
JF
Department of Medicinal Biochemistry, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Miller
D B
DB
O'Callaghan
J P
JP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine