Identifying Lipid Changes in Nerve Tissue as a Result of Dichloroacetate Treatment using IP-MALDI Coupled to a Linear Ion Trap

摘要

The ability of mitochondria to efficiently convert substrate fuels into energy is a requisite for life among eukaryotic organisms. Interruption of this process can lead to several clinical complications, including lactic acidosis. Congenital forms of lactic acidosis arise from duplications, deletions, or point mutations in genes coding for respiratory chain and other mitochondrial enzymes. This results in an accumulation of lactic acid and hydrogen ions in blood, urine, and/or cerebrospinal fluid. Often this leads to neurological and neuromuscular deterioration and, in the most extreme cases, death. The investigational drug dichloroacetate (DCA) has been used in the chronic treatment of congenital lactic acidosis. However, its use has been mitigated in some patients by reversible peripheral neuropathy (PN), which has also been demonstrated in dosed animals at exposure levels >=50 mg/kg/day for several weeks or months. We hypothesized that DCA-associated PN could be due in part to a change in lipids in both the central and peripheral nervous systems, and it is the focus of this study to characterize changes in these lipids.