domoic-acid and Mitochondrial-Diseases

domoic-acid has been researched along with Mitochondrial-Diseases* in 1 studies

Other Studies

1 other study(ies) available for domoic-acid and Mitochondrial-Diseases

ArticleYear
Ursolic acid improves domoic acid-induced cognitive deficits in mice.
    Toxicology and applied pharmacology, 2013, Sep-01, Volume: 271, Issue:2

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders.

    Topics: Animals; Animals, Genetically Modified; Cognition Disorders; Cyclooxygenase Inhibitors; Dependovirus; Fluorescent Antibody Technique; Forkhead Box Protein O1; Forkhead Transcription Factors; Genetic Vectors; Hippocampus; Kainic Acid; Male; Maze Learning; Mice; Mice, Inbred ICR; Mitochondrial Diseases; Neuromuscular Depolarizing Agents; Oncogene Protein v-akt; Oxidative Stress; Phosphatidylinositol 3-Kinases; Psychomotor Performance; Signal Transduction; Triterpenes; Ursolic Acid

2013