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Valproic Acid Alters Activities of Key Enzymes of Glucose Oxidative Metabolism, Citric Acid Cycle and Neurotransmitter Synthesis in Embryonic Rat Brain
Author(s) -
Triyasakorn Korawin,
Lai James C.K.,
Awale Prabha
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05917
Subject(s) - valproic acid , citric acid cycle , glutamate receptor , medicine , biology , endocrinology , lactate dehydrogenase , pharmacology , biochemistry , enzyme , metabolism , epilepsy , neuroscience , receptor
Although studies have investigated the role of gamma‐aminobutyric acid (GABA)ergic signaling in rodent neural development and behaviors relevant to autism, the energetics that underlie neural developmental changes are poorly understood. Here, we employed a valproic acid (VPA) rat model of autism to investigate the effects of VPA treatment on key enzymes of glucose oxidative metabolism and citric acid cycle (namely lactate dehydrogenase (LDH), malate dehydrogenase (MDH) and glutamate dehydrogenase (GDH)) in rat brain. Pregnant Wistar rats were administered 600 mg/kg of VPA by intraperitoneal injection on day 12.5 of gestation and embryonic (E) day 15 and E17 rat brains were assayed for the activities of the enzymes. Both E15 and E17 male and female rat models of VPA‐induced autism showed significantly changed whole brain activities of the enzymes studied compared to the corresponding values in control rats. The dysregulated GDH activity could alter the excitatory‐inhibitory balance in the brain of embryonic rats during development. Thus, our findings may have pathophysiological/pathogenic implications in autism and may ultimately lead to the discovery of new therapeutic target(s) for autism. Support or Funding Information Seed Grant Idaho State University College of Pharmacy