PMID- 25584778
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20210716
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 59
DP  - 2015 Jun 3
TI  - Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal 
      cortex signalling molecules involved in recognition memory.
PG  - 68-75
LID - S0278-5846(15)00005-6 [pii]
LID - 10.1016/j.pnpbp.2015.01.004 [doi]
AB  - 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 10mg/kg/day BM orally for 21weeks. 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Camer, Danielle
AU  - Camer D
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia.
FAU - Yu, Yinghua
AU  - Yu Y
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia.
FAU - Szabo, Alexander
AU  - Szabo A
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia; ANSTO LifeSciences, Australian Nuclear Science and Technology 
      Organisation, NSW 2234, Australia.
FAU - Fernandez, Francesca
AU  - Fernandez F
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia; Faculty of Social Sciences, University of Wollongong, 
      Wollongong, NSW 2522, Australia; Schizophrenia Research Institute, Sydney, NSW 
      2522, Australia.
FAU - Dinh, Chi H L
AU  - Dinh CHL
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia.
FAU - Huang, Xu-Feng
AU  - Huang XF
AD  - Centre for Translational Neuroscience, School of Medicine, University of 
      Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 
      2522, Australia. Electronic address: xhuang@uow.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150110
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Neuroprotective Agents)
RN  - 10028-17-8 (Tritium)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - CEG1Q6OGU1 (bardoxolone methyl)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Diet, High-Fat/*adverse effects
MH  - Disease Models, Animal
MH  - Dizocilpine Maleate/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Exploratory Behavior/drug effects
MH  - Male
MH  - *Memory Disorders/etiology/pathology/prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/pharmacokinetics
MH  - Oleanolic Acid/*analogs & derivatives/therapeutic use
MH  - Prefrontal Cortex/*drug effects/metabolism
MH  - Protein Binding/drug effects
MH  - Recognition, Psychology/*drug effects
MH  - Signal Transduction/*drug effects
MH  - Statistics, Nonparametric
MH  - Tritium/pharmacokinetics
OTO - NOTNLM
OT  - Bardoxolone methyl
OT  - Hippocampus
OT  - Obesity
OT  - Prefrontal cortex
OT  - Recognition memory
EDAT- 2015/01/15 06:00
MHDA- 2015/11/17 06:00
CRDT- 2015/01/14 06:00
PHST- 2014/09/24 00:00 [received]
PHST- 2014/12/22 00:00 [revised]
PHST- 2015/01/07 00:00 [accepted]
PHST- 2015/01/14 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
AID - S0278-5846(15)00005-6 [pii]
AID - 10.1016/j.pnpbp.2015.01.004 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:68-75. doi: 
      10.1016/j.pnpbp.2015.01.004. Epub 2015 Jan 10.