PMID- 23373812
OWN - NLM
STAT- MEDLINE
DCOM- 20130620
LR  - 20220408
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 125
IP  - 3
DP  - 2013 May
TI  - Neuroprotective effects of PPAR-gamma agonist rosiglitazone in N171-82Q mouse model 
      of Huntington's disease.
PG  - 410-9
LID - 10.1111/jnc.12190 [doi]
AB  - Huntington's disease (HD) is a devastating genetic neurodegenerative disease 
      caused by CAG trinucleotide expansion in the exon-1 region of the huntingtin 
      gene. Currently, no cure is available. It is becoming increasingly apparent that 
      mutant Huntingtin (HTT) impairs metabolic homeostasis and causes transcriptional 
      dysregulation. The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a 
      transcriptional factor that plays a key role in regulating genes involved in 
      energy metabolism; recent studies demonstrated that PPAR-gamma activation prevented 
      mitochondrial depolarization in cells expressing mutant HTT and attenuated 
      neurodegeneration in various models of neurodegenerative diseases. 
      PPAR-gamma-coactivator 1alpha (PGC-1 alpha) transcription activity is also impaired by mutant 
      HTT. We now report that the PPAR-gamma agonist, rosiglitazone (RSG), significantly 
      attenuated mutant HTT-induced toxicity in striatal cells and that the protective 
      effect of RSG is mediated by activation of PPAR-gamma. Moreover, chronic 
      administration of RSG (10 mg/kg/day, i.p) significantly improved motor function 
      and attenuated hyperglycemia in N171-82Q HD mice. RSG administration rescued 
      brain derived neurotrophic factor(BDNF) deficiency in the cerebral cortex, and 
      prevented loss of orexin-A-immunopositive neurons in the hypothalamus of N171-82Q 
      HD mice. RSG also prevented PGC-1alpha reduction and increased Sirt6 protein levels 
      in HD mouse brain. Our results suggest that modifying the PPAR-gamma pathway plays a 
      beneficial role in rescuing motor function as well as glucose metabolic 
      abnormalities in HD.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Jin, Jing
AU  - Jin J
AD  - Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns 
      Hopkins University School of Medicine, Baltimore, Maryland, USA.
FAU - Albertz, Jennifer
AU  - Albertz J
FAU - Guo, Zhihong
AU  - Guo Z
FAU - Peng, Qi
AU  - Peng Q
FAU - Rudow, Gay
AU  - Rudow G
FAU - Troncoso, Juan C
AU  - Troncoso JC
FAU - Ross, Christopher A
AU  - Ross CA
FAU - Duan, Wenzhen
AU  - Duan W
LA  - eng
GR  - P30 DK079637/DK/NIDDK NIH HHS/United States
GR  - R21 NS072344/NS/NINDS NIH HHS/United States
GR  - NS072344/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130305
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glutamates)
RN  - 0 (HCRT protein, human)
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Orexins)
RN  - 0 (PPAR gamma)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 3.5.1.- (SIRT6 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Anilides/pharmacology
MH  - Animals
MH  - Brain/drug effects/enzymology/pathology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Glutamates/genetics
MH  - Humans
MH  - Huntingtin Protein
MH  - Huntington Disease/complications/*drug therapy/genetics/pathology
MH  - Hyperglycemia/drug therapy/etiology
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Movement Disorders/drug therapy/etiology
MH  - Nerve Tissue Proteins/genetics
MH  - Neurons/*drug effects/metabolism
MH  - Neuropeptides/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Orexins
MH  - PPAR gamma/antagonists & inhibitors
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - RNA, Messenger/metabolism
MH  - Rosiglitazone
MH  - Sirtuins/metabolism
MH  - Thiazolidinediones/pharmacology/*therapeutic use
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors
MH  - Transfection
MH  - Trinucleotide Repeat Expansion/genetics
PMC - PMC3642978
MID - NIHMS443117
COIS- All authors have no conflict of interest to declare.
EDAT- 2013/02/05 06:00
MHDA- 2013/06/21 06:00
PMCR- 2014/05/01
CRDT- 2013/02/05 06:00
PHST- 2012/10/23 00:00 [received]
PHST- 2013/01/30 00:00 [revised]
PHST- 2013/01/30 00:00 [accepted]
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/06/21 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - 10.1111/jnc.12190 [doi]
PST - ppublish
SO  - J Neurochem. 2013 May;125(3):410-9. doi: 10.1111/jnc.12190. Epub 2013 Mar 5.