PMID- 19384567
OWN - NLM
STAT- MEDLINE
DCOM- 20100111
LR  - 20211020
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 15
IP  - 4
DP  - 2009 May
TI  - Neuroprotective effect of ghrelin in the 
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease 
      by blocking microglial activation.
PG  - 332-47
LID - 10.1007/s12640-009-9037-x [doi]
AB  - Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a 
      (GHS-R1a) and is produced and released mainly from the stomach. It was recently 
      demonstrated that ghrelin can function as a neuroprotective factor by inhibiting 
      apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes 
      nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest 
      that activated microglia actively participate in the pathogenesis of Parkinson's 
      disease (PD) neurodegeneration. However, the role of microglia in the 
      neuroprotective properties of ghrelin is still unknown. Here we show that, in the 
      mouse MPTP PD model generated by an acute regimen of MPTP administration, 
      systemic administration of ghrelin significantly attenuates the loss of 
      substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic 
      fibers through the activation of GHS-R1a. We also found that ghrelin reduced 
      nitrotyrosine levels and improved the impairment of rota-rod performance. Ghrelin 
      prevents MPTP-induced microglial activation in the SNpc and striatum, the 
      expression of pro-inflammatory molecules tumor necrosis factor alpha (TNF-alpha) 
      and interleukin-1beta (IL-1beta), and the activation of inducible nitric oxide 
      synthase. The inhibitory effect of ghrelin on the activation of microglia appears 
      to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in 
      stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial 
      cells. Finally, in vitro administration of ghrelin prevented 
      1-methyl-4-phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, 
      microglial activation, and the subsequent release of TNF-alpha, IL-1beta, and 
      nitrite in mesencephalic cultures. Our data indicate that ghrelin may act as a 
      survival factor for dopaminergic neurons by functioning as a 
      microglia-deactivating factor and suggest that ghrelin may be a valuable 
      therapeutic agent for neurodegenerative diseases such as PD.
FAU - Moon, Minho
AU  - Moon M
AD  - Department of Pharmacology and Medical Research Center for Bioreaction to ROS and 
      Biomedical Science Institute, Kyunghee University School of Medicine, Seoul, 
      130-701, Korea.
FAU - Kim, Hyo Geun
AU  - Kim HG
FAU - Hwang, Lakkyong
AU  - Hwang L
FAU - Seo, Ji-Hyung
AU  - Seo JH
FAU - Kim, Sehee
AU  - Kim S
FAU - Hwang, Sunyoung
AU  - Hwang S
FAU - Kim, Soonyong
AU  - Kim S
FAU - Lee, Dahm
AU  - Lee D
FAU - Chung, Hyunju
AU  - Chung H
FAU - Oh, Myung Sook
AU  - Oh MS
FAU - Lee, Kyung-Tae
AU  - Lee KT
FAU - Park, Seungjoon
AU  - Park S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090317
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Ghrelin)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitrites)
RN  - 0 (Receptors, Ghrelin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Cells, Cultured
MH  - Corpus Striatum/metabolism
MH  - Disease Models, Animal
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation/drug effects
MH  - Ghrelin/*pharmacology
MH  - Gliosis/chemically induced/prevention & control
MH  - Interleukin-1beta/metabolism
MH  - MPTP Poisoning/drug therapy/pathology/*physiopathology
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mesencephalon/cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*drug effects
MH  - Motor Activity/drug effects
MH  - Nerve Degeneration/chemically induced/prevention & control
MH  - Neurons/drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitrites/metabolism
MH  - Rats
MH  - Receptors, Ghrelin/genetics/metabolism
MH  - Tandem Mass Spectrometry/methods
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tyrosine 3-Monooxygenase/genetics/metabolism
EDAT- 2009/04/23 09:00
MHDA- 2010/01/12 06:00
CRDT- 2009/04/23 09:00
PHST- 2008/09/17 00:00 [received]
PHST- 2009/02/18 00:00 [accepted]
PHST- 2009/02/18 00:00 [revised]
PHST- 2009/04/23 09:00 [entrez]
PHST- 2009/04/23 09:00 [pubmed]
PHST- 2010/01/12 06:00 [medline]
AID - 10.1007/s12640-009-9037-x [doi]
PST - ppublish
SO  - Neurotox Res. 2009 May;15(4):332-47. doi: 10.1007/s12640-009-9037-x. Epub 2009 
      Mar 17.