Mitochondrial-Dependent Ca2+Handling in Huntington's Disease Striatal Cells: Effect of Histone Deacetylase Inhibitors

• DOI: 10.1523/jneurosci.3004-06.2006
• Publication Date: 2006-10-25T18:22:01Z
• Authors: Jorge M. A. Oliveira; Sylvia Chen; Sandra Almeida; Rebeccah Riley; Jorge Gonçalves; Catarina R. Oliveira; Michael R. Hayden; David G. Nicholls; Lisa M. Ellerby; A. Cristina Rego
• Keywords: Sodium butyrate; Trichostatin A; Huntingtin Protein

Evidence suggests that neuronal dysfunction in Huntington's disease (HD) striatum involves deficits mitochondrial function and Ca 2+ handling. However, the relationship between mitochondria handling has been incompletely studied intact HD striatal cells. Treatment with histone deacetylase (HDAC) inhibitors reduces cell death models, but effects of this promising therapy on cellular are mostly unknown. Here, we use real-time functional imaging intracellular membrane potential to explore role situ Immortalized (ST Hdh ) cells neurons from transgenic mice, expressing full-length mutant huntingtin (Htt), were used model HD. We show (1) active glycolysis ST occludes as well inhibitors, (2) absence critically dependent oxidative phosphorylation for energy-dependent handling, (3) expression Htt is associated mitochondrial-dependent can be ameliorated by treatment HDAC (treatment trichostatin A or sodium butyrate decreases proportion losing homeostasis after -ionophore challenging, accelerates restoration challenged NMDA), (4) different response patterns NMDA receptor activation exhibit average somatic areas differentially affected suggesting subpopulation state specificity. These findings indicate neuroprotection induced more efficient thus improving ability cope excitotoxic stimuli.