Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

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dc.contributor.authorCamer, Den_AU
dc.contributor.authorYu, YHen_AU
dc.contributor.authorFernandez, Fen_AU
dc.contributor.authorDinh, CHLen_AU
dc.contributor.authorHuang, XFen_AU
dc.contributor.authorSzabo, Aen_AU
dc.date.accessioned2017-05-15T01:33:24Zen_AU
dc.date.available2017-05-15T01:33:24Zen_AU
dc.date.issued2015-06-03en_AU
dc.description.abstractHigh fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood–brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF diet-induced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus.© 2015, Elsevier Inc.en_AU
dc.identifier.citationCamer, D., Yu, Y., Szabo, A., Fernandez, F., Dinh, C. H. L., & Huang, X. F. (2015). Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 59, 68-75. doi:10.1016/j.pnpbp.2015.01.004en_AU
dc.identifier.govdoc8224en_AU
dc.identifier.issn1878-4216en_AU
dc.identifier.journaltitleProgress in Neuro-Psychopharmacology & Biological Psychiatryen_AU
dc.identifier.pagination68-75en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.pnpbp.2015.01.004en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8700en_AU
dc.identifier.volume59en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectMiceen_AU
dc.subjectDieten_AU
dc.subjectBrainen_AU
dc.subjectInflammationen_AU
dc.subjectHippocampusen_AU
dc.subjectMetabolic diseasesen_AU
dc.titleBardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memoryen_AU
dc.typeJournal Articleen_AU
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