Myogenic Satellite Cells, Mitochondrial DNA, Neuronal Progenitor Cells, Perineuronal Satellite Cells, and Reduced Folates

The authors of this article [Taivassalo and Haller, 2004: (http://www.ncbi.nlm.nih.gov/pubmed/15576055)] discuss the possibility that myogenic satellite cells in skeletal muscles, some of which are actually CD34+ and respond to erythropoietin, may be able to actually donate wild-type mtDNA to myocytes and reverse heteroplasmy, to some extent, in myocytes in people with mitochondrial disorders. The satellite cells are mitotic and may have some pluripotency, as stem cells, but the authors have found that resistance exercise (weight training), in particular, stimulates satellite cell proliferation and reverses some of the heteroplasmy of mtDNA in the skeletal muscle myocytes of people with mitochondrial myopathies. It's because the mitotic cells tend to not accumulate as much mutant mtDNA and are like a "reservoir" of wild-type mtDNA that persisted during development.

I wonder if something similar might occur in the brain, in which either perineuronal satellite cells or neural progenitor cells might either donate mtDNA to neurons or undergo apoptosis and provide purines (and pyrimidines) to adjacent cells, thereby supporting mtDNA turnover and transcription in postmitotic neurons. There's constant turnover of mtDNA in cardiac myocytes and neurons, and I think the "half-life" of mtDNA turnover is about 7 days in rodents. Presumably it's less rapid in humans. The reason I suggest this nucleotide "donation" effect, specifically with purines, is that purines can't just disappear through apoptosis. I think oxidatively-modified bases, for example, such as modified deoxyguanosine (I forget the chemical name of the common modification), have to be excreted renally. And I think there might actually be a low activity of xanthine oxidase in the brain itself, even though there's a really high level of xanthine oxidase activity in the endothelial cells lining the cerebral blood vessels. In tumor lysis syndrome, for example, the lysis of cells from radiation therapy or other causes can produce acute urate nephropathy, which is uric acid-induced acute renal failure. That's a very extreme condition, and uric acid is probably not the only nephrotoxic mediator that is produced by radiation therapy. But purines simply cannot be degraded magically, and I wonder if the rate of degradation of purines, in apoptotic perineuronal satellite cells or poorly-differentiated neural progenitor cells, might be slow enough to allow "purine-buffering," via the accumulation of purines in the extracellular fluid, by apoptotic-cell-derived adenosine, inosine, guanosine, or their nucleotides (monophosphates, diphosphates, etc.). Here's an article that discusses perineuronal satellite cells and different pathways by which subventricular-zone-derived and dentate-gyrus-derived neural progenitor cells are trafficked: [Kuhn et al., 1997: (http://www.jneurosci.org/cgi/content/full/17/15/5820) (http://www.ncbi.nlm.nih.gov/pubmed/9221780?dopt=Abstract)]. Depletion of folates from the brain has been shown to reduce the proliferation of neural progenitor cells, and reduced folates, by virtue of their capacity to cross the blood-CSF barrier, could contribute to neuronal repair by some of those types of mechanisms.