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Kilbourn MR, Charalambous A, Frey KA, Sherman P, Higgins DS Jr, Greenamyre JT: Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I. Ann Neurol. 1988 Mar;23(3):287-94. The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C] dihydrorotenol ([11C] DHROL: 40%) and in vitro binding of [3H] dihydrorotenone ([3H] DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C] DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C] DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C] iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases. |
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