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CHARACTERIZATION OF THE ASTROCYTE RESPONSE TO INJURY USING THE DOPAMINERGIC NEUROTOXICANT, 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE
Citation:
O'Callaghan, J., D. Miller, AND J. Reinhard. CHARACTERIZATION OF THE ASTROCYTE RESPONSE TO INJURY USING THE DOPAMINERGIC NEUROTOXICANT, 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/231 (NTIS PB91117077), 1990.
Description:
The amount of glial fibrillary acidic protein (GFAP), an astrocyte protein, increases following injury of the CNS. e used a radioimmunoassay of GFAP to characterize the astrocytic response to injury resulting from exposure to the dopaminergic neurotoxicant, 1-methyl-1,2,3,6-tetrahydropyridine (MPTP). ingle administration of MPTP to the C57BL/6 mouse resulted in more than a 3-fold increase in GFAP within 48 hours, followed by a decline to baseline at 3 weeks. ecrease in the amount of tyrosine hydroxylase (TH), a marker of nigrostriatal dopaminergic neurons, precede the rise in GPAP. he concentration of DARPP-32, a phosphoprotein localized to striatal neurons receiving dopaminergic input, was not affected by MPTP. rotecting the dopaminergic neurons from the neurotoxic metabolite of MPTP, 1-methyl-4- phenylpyridinium (MPP+), either by blocking its formation or by preventing its uptake into dopamine neurons, completely blocked the increase in GFAP. loodborne or brain-derived interleukin 1 (IL-1), a known astrocyte mitogen, did not appear to mediate the effects of MPTP on GPAP. ogether, these findings suggested that factors emanating from dopamine neurons initiate the astrocyte response to MPTP.