POSSIBLE RELATIONSHIP BETWEEN CONDITIONS ASSOCIATED WITH CHRONIC HYPOXIA AND BRAIN MITOCHONDRIAL-DNA DELETIONS

The brain relies heavily on aerobic metabolism which requires function al mitochondria. Mitochondria are subcellular organelles with their ow n genome which codes for 13 essential protein subunits. By employing P CR assays to examine brain tissue from 43 age-comparable individuals ( between ages 34 and 73), we found a correlation between mitochondrial DNA deletion mutations, mtDNA(4977) deletions, and conditions associat ed with chronic hypoxia. In prior studies, utilizing only 6 to 12 clin ical samples, mtDNA(4977) deletions were reported to increase in speci fic regions of the brain with aging. However, we found 12-fold and 5-f old higher levels of mtDNA(4977) deletions in the putamen and the supe rior frontal gyrus of the cortex, respectively, from individuals who h ad conditions associated with chronic hypoxia when compared with indiv iduals without evidence of such conditions. These findings suggest tha t chronic hypoxia should be more closely examined in the pathophysiolo gy of central nervous system diseases.