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Chunk #21 — Intrinsic regulation of oligodendrocyte responses — Age

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Chronic oligodendrocyte injury in central nervous system pathologies.
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With regards to metabolism, under optimal conditions, adult rat OLs preferentially use glycolysis whereas in development, OPCs and newly differentiated OLs mainly utilize oxidative phosphorylation to produce Adenosine 5′-triphosphate (ATP). We observed that human mature OLs also preferentially use glycolysis but overall have a significantly lower rate of metabolic activity compared to their rat counterparts100. Neumann et al compared metabolic properties of OPCs in culture derived from young versus aged adult rats, and found lower ATP levels and cellular respiration in the latter, likely reflecting mitochondrial dysfunction101. Our in vitro studies indicated that mature human OLs derived from young-middle aged adult brain undergo non-apoptotic death in response to metabolic stress culture conditions in vitro19; conversely, OLs and progenitors from pediatric and fetal sources show a measurable apoptotic response, with differences ascribed to relative expression of effector versus protective members of the BCL-2 family65.