Increased mitochondrial permeability in response to intrastriatal N-methyl-D-aspartate: detection based on accumulation of radiolabel from [3H]deoxyglucose.
Induction of the mitochondrial permeability transition has been proposed as an important contributor to cell loss in several neurological disorders, but the evidence that this change can develop in cells in the intact mature brain is largely indirect. In this study, we have tested whether an intrastriatal injection of N-methyl-D-aspartate results in increases in inner membrane permeability that can be detected from mitochondrial accumulation of metabolites of 3H-deoxyglucose previously taken up by brain cells. An increase in incorporation of deoxyglucose metabolites was found in mitochondria prepared from the striatum but not from cerebral cortex distant from the injection site. This change developed more than 8 h after treatment with N-methyl-D-aspartate and is consistent with the induction of the permeability transition as a late change in the progression to irreversible neuronal damage in response to this excitotoxic insult. At earlier times, the restricted permeability of the inner mitochondrial membrane was apparently preserved, at least sufficiently to prevent significant diffusion of metabolites between the cytoplasm and the matrix.
Zaidan
Emad
E
Department of Medical Biochemistry, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
Nilsson
Michael
M
Sims
Neil R
NR
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D008845:Microinjections; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000378:metabolism* / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014316:Tritium
D014316:Tritium; D016202:N-Methylaspartate; D016572:Cyclosporine; D003847:Deoxyglucose; D002950:Citrate (si)-Synthase