Hamilton, JamesPellman, Jessica J.Brustovetsky, TatianaHarris, Robert A.Brustovetsky, Nickolay2018-05-042018-05-042016-07-01Hamilton, J., Pellman, J. J., Brustovetsky, T., Harris, R. A., & Brustovetsky, N. (2016). Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington’s disease. Human Molecular Genetics, 25(13), 2762–2775. http://doi.org/10.1093/hmg/ddw133https://hdl.handle.net/1805/16061Alterations in oxidative metabolism and defects in mitochondrial Ca2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca2+ Overall, our data argue against respiratory deficiency and impaired Ca2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice.en-USPublisher PolicyOxygen -- MetabolismMitochondriaBrain -- MetabolismHuntington's diseaseOxidative stressNervous system -- Degeneration -- PathophysiologyArticle