visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure海马神经元的动态可视化的时空能量kainate-induced发作期间质谱.pdfVIP

Visualization of Spatiotemporal Energy Dynamics of Hippocampal Neurons by Mass Spectrometry during a Kainate-Induced Seizure 1 2 1 Yuki Sugiura , Ryo Taguchi , Mitsutoshi Setou * 1 Department of Molecular Anatomy, Hamamatsu Medical School, Higashi-ku, Hamamatsu, Shizuoka, Japan, 2 Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Abstract We report the use of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry combined with capillary electrophoresis (CE) mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels—especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron- selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully reve