ANSTO Publications Online >
Journal Publications >
Journal Articles >

Please use this identifier to cite or link to this item: http://apo.ansto.gov.au/dspace/handle/10238/8700

Title: Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory
Authors: Camer, D
Yu, Y
Fernandez, F
Dinh, CHL
Huang, X-F
Keywords: FATS
PLASTICITY
MICE
MOLECULES
CEREBRAL CORTEX
PROTEINS
Issue Date: 3-Jun-2015
Publisher: Elsevier
Citation: Camer, 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: http://dx.doi.org/10.1016/j.pnpbp.2015.01.004
Abstract: High 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.
URI: http://dx.doi.org/10.1016/j.pnpbp.2015.01.004
http://apo.ansto.gov.au/dspace/handle/10238/8700
ISSN: 0278-5846
Appears in Collections:Journal Articles

Files in This Item:

There are no files associated with this item.

Items in APO are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback