Neuroglial responses to the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse striatum.
We have studied the reactive responses of both astrocytes and microglia to dopaminergic denervation of the striatum by MPTP. Following MPTP treatment, increased GFAP immunoreactivity reached a peak at 2 days and persisted for at least 6 weeks. Immunoreactivity to vimentin was also markedly increased in astrocytes 48 h after MPTP treatment. Striatal laminin immunoreactivity, however, appeared to be unaffected by drug treatment. GFAP protein levels increased to 196% and 321% of control 24 and 48 hours after MPTP treatment, respectively. Concomitantly, GFAP mRNA levels increased to 560% and 1620% of control, respectively. These reactive changes in striatal astrocytes in response to MPTP treatment were also accompanied by a reactive microglial response as evidenced by increased immunohistochemical visualization of striatal microglia using antibodies to Mac-1. Our results and those reported previously by O'Callaghan et al., strongly suggest that MPTP-induced reactive gliosis in mouse striatum is associated with reactive microglia, albeit without increased interleukin-1 beta.
Francis
J W
JW
Department of Anatomy, University of Maryland School of Medicine, Baltimore 21201.
Von Visger
J
J
Markelonis
G J
GJ
Oh
T H
TH
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000954:Antigens, Surface; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D009419:Nerve Tissue Proteins; D014746:Vimentin; D012313:RNA; D014446:Tyrosine 3-Monooxygenase