PMID- 29721854
OWN - NLM
STAT- MEDLINE
DCOM- 20190401
LR  - 20200225
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 1
DP  - 2019 Jan
TI  - Abscisic Acid Supplementation Rescues High Fat Diet-Induced Alterations in 
      Hippocampal Inflammation and IRSs Expression.
PG  - 454-464
LID - 10.1007/s12035-018-1091-z [doi]
AB  - Accumulated evidence indicates that neuroinflammation induces insulin resistance 
      in the brain. Moreover, both processes are intimately linked to neurodegenerative 
      disorders, including Alzheimer's disease. Potential mechanisms underlying insulin 
      resistance include serine phosphorylation of the insulin receptor substrate (IRS) 
      or insulin receptor (IR) misallocation. However, only a few studies have focused 
      on IRS expression in the brain and its modulation in neuroinflammatory processes. 
      This study used the high-fat diet (HFD) model of neuroinflammation to study the 
      alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS 
      expressions in the hippocampus. We observed that HFD effectively reduced mRNA and 
      protein IRS2 expression. In contrast, a HFD induced the upregulation of the IRS1 
      mRNA levels, but did not alter an IR and IGF1R expression. As expected, we 
      observed that a HFD increased hippocampal tumor necrosis factor alpha (TNFalpha) and 
      amyloid precursor protein (APP) levels while reducing brain-derived neurotrophic 
      factor (BDNF) expression and neurogenesis. Interestingly, we found that TNFalpha 
      correlated positively with IRS1 and negatively with IRS2, whereas APP levels 
      correlated positively only with IRS1 but not IRS2. These results indicate that 
      IRS1 and IRS2 hippocampal expression can be affected differently by HFD-induced 
      neuroinflammation. In addition, we aimed to establish whether abscisic acid (ABA) 
      can rescue hippocampal IRS1 and IRS2 expression, as we had previously shown that 
      ABA supplementation prevents memory impairments and improves neuroinflammation 
      induced by a HFD. In this study, ABA restored HFD-induced hippocampal 
      alterations, including IRS1 and IRS2 expression, TNFalpha, APP, and BDNF levels and 
      neurogenesis. In conclusion, this study highlights different regulations of 
      hippocampal IRS1 and IRS2 expression using a HFD, indicating the important 
      differences of these scaffolding proteins, and strongly supports ABA therapeutic 
      effects.
FAU - Ribes-Navarro, Alberto
AU  - Ribes-Navarro A
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain.
FAU - Atef, Mariam
AU  - Atef M
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain.
FAU - Sanchez-Sarasua, Sandra
AU  - Sanchez-Sarasua S
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain.
FAU - Beltran-Bretones, Maria Teresa
AU  - Beltran-Bretones MT
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain.
FAU - Olucha-Bordonau, Francisco
AU  - Olucha-Bordonau F
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain.
FAU - Sanchez-Perez, Ana Maria
AU  - Sanchez-Perez AM
AD  - Department of Medicine, University of Jaume I, Castellon de la Plana, Spain. 
      sanchean@uji.es.
LA  - eng
GR  - AICO/2015/042/Generalitat Valenciana/
PT  - Journal Article
DEP - 20180502
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 72S9A8J5GW (Abscisic Acid)
SB  - IM
EIN - Mol Neurobiol. 2019 Feb 26;:. PMID: 30806955
MH  - Abscisic Acid/*pharmacology
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Diet, High-Fat
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/drug effects/*metabolism/*pathology
MH  - Inflammation/*pathology
MH  - Insulin Receptor Substrate Proteins/genetics/*metabolism
MH  - Male
MH  - Neurogenesis/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Weight Gain
OTO - NOTNLM
OT  - APP
OT  - BDNF
OT  - Hippocampus
OT  - Insulin resistance
OT  - Neurogenesis
OT  - Neuroinflammation
EDAT- 2018/05/04 06:00
MHDA- 2019/04/02 06:00
CRDT- 2018/05/04 06:00
PHST- 2018/01/09 00:00 [received]
PHST- 2018/04/17 00:00 [accepted]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/04/02 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
AID - 10.1007/s12035-018-1091-z [pii]
AID - 10.1007/s12035-018-1091-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Jan;56(1):454-464. doi: 10.1007/s12035-018-1091-z. Epub 2018 
      May 2.