Variation in the frequency of complex forms of mitochondrial DNA in different brain regions of senescent mice.

It was shown previously that the frequency of an aberrant form of mitochondrial DNA (mtDNA), double-sized circular molecules or circular dimers, increased significantly in the brain of senescent mice, to about 2% versus less than 0.1% in the brain of adult mice. To follow up these observations, we isolated total mtDNA from 6 different brain regions of 29-month-old male BALB/c mice and examined it for the occurrence of circular dimers and other complex forms by electron microscopy. There was a statistically highly significant variability in the occurrence of circular dimer mtDNA among the 6 brain regions. The frequencies of circular dimers were: medulla, 3.3%; cortex, 1.7%; midbrain, 1.1%; cerebellum, 0.9%; hippocampus, 0.5%; and striatum, 0.2%. The frequency of catenated (topologically interlinked) molecules varied only slightly, from 4 to 6%. On the basis of the available literature, a correlation appears to exist between age-related tissue pathology of the mouse brain and the increased incidence of circular dimer mtDNA. Although no cause-effect relationships can be established, it is suggested that the frequency of circular dimer mtDNA may be a useful marker in assessing the general physiological condition of the aging brain.