Moving Metabolism to Make Inroads in a Model of Mitochondrial Epilepsy.

Moving Metabolism to Make Inroads in a Model of Mitochondrial Epilepsy. Epilepsy Curr. 2019 Sep 09;:1535759719873360 Authors: Lyman KA, Chetkovich DM Abstract Brain Metabolism Modulates Neuronal Excitability in a Mouse Model of Pyruvate Dehydrogenase Deficiency Jakkamsetti V, Marin-Valencia I, Ma Q, Good LB, Terrill T, Raiasekaran K, Pichumani K, Khemtong C, Hooshyar MA, Sundarrajan C, Patel MS, Bachoo RM, Malloy CR, Pascual JM. Sci Transl Med. 2019;11(480). pii: eaan0457. doi:10.1126/scitranslmed.aan0457. Glucose is the ultimate substrate for most brain activities that use carbon, including synthesis of the neurotransmitters glutamate and γ-aminobutyric acid via mitochondrial tricarboxylic acid (TCA) cycle. Brain metabolism and neuronal excitability are thus interdependent. However, the principles that govern their relationship are not always intuitive because heritable defects of brain glucose metabolism are associated with the paradoxical coexistence, in the same individual, of episodic neuronal hyperexcitation (seizures) with reduced basal cerebral electrical activity. One such prototypic disorder is pyruvate dehydrogenase (PDH) deficiency (PDHD). Pyruvate dehydrogenase is central to metabolism because it steers most of the glucose-derived flux into the TCA cycle. To better understand the pathophysiology of PDHD, we generated mice with brain-specific reduced PDH activity that paralleled salient human disease features, including ...
Source: Epilepsy Curr - Category: Neurology Authors: Tags: Epilepsy Curr Source Type: research