PMID- 15499605
OWN - NLM
STAT- MEDLINE
DCOM- 20050217
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 55
IP  - 1
DP  - 2005 Jan
TI  - Selective alterations of gene expression in mice induced by MPTP.
PG  - 45-51
AB  - 1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin 
      that produces striatal dopamine depletion resulting in parkinsonism like symptoms 
      in humans and is, therefore, used to generate animal models for Parkinson's 
      disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3x20 
      mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours 
      after the last injection and brain tissue was collected for analysis. Significant 
      decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed 
      after MPTP treatment. MPTP also reduced protein expression of tyrosine 
      hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective 
      genes of the dopaminergic system in the substantia nigra. Our data demonstrated 
      that MPTP significantly decreased gene expression of TH, dopamine transporter 
      (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of 
      dopamine concentration changes and protein expression after MPTP treatment. 
      Although a significant decrease of DA metabolites was observed in striatum, there 
      was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol 
      O-methyltransferase (COMT), indicating that these changes might be simply a 
      consequence of reduced monoamine levels. In addition, gene expression of 
      alpha-synuclein was also decreased with MPTP treatment, but there was no change 
      in beta-synuclein and parkin. This is the first study using real-time PCR to 
      indicate that MPTP selectively alters gene expression and provides information 
      for clinical studies in PD. Future studies will focus on gene expression of other 
      pathways that may be affected by MPTP treatment and investigation of gene 
      expression in specific cell types in vivo using LCM technology.
CI  - copyright (c) 2004 Wiley-Liss, Inc.
FAU - Xu, Z
AU  - Xu Z
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, 
      USA.
FAU - Cawthon, D
AU  - Cawthon D
FAU - McCastlain, K A
AU  - McCastlain KA
FAU - Slikker, W Jr
AU  - Slikker W Jr
FAU - Ali, S F
AU  - Ali SF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Dopamine Agents)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc6a3 protein, mouse)
RN  - 0 (Snca protein, mouse)
RN  - 0 (Sncb protein, mouse)
RN  - 0 (Synucleins)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (alpha-Synuclein)
RN  - 0 (beta-Synuclein)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Corpus Striatum/drug effects
MH  - Dopamine/metabolism
MH  - Dopamine Agents/*pharmacology
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Gene Expression/*drug effects
MH  - Gene Expression Regulation/*drug effects
MH  - Homovanillic Acid/metabolism
MH  - Male
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - Membrane Transport Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - RNA, Messenger
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Synucleins
MH  - Tyrosine 3-Monooxygenase/genetics/metabolism
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - alpha-Synuclein
MH  - beta-Synuclein
EDAT- 2004/10/23 09:00
MHDA- 2005/02/18 09:00
CRDT- 2004/10/23 09:00
PHST- 2004/10/23 09:00 [pubmed]
PHST- 2005/02/18 09:00 [medline]
PHST- 2004/10/23 09:00 [entrez]
AID - 10.1002/syn.20089 [doi]
PST - ppublish
SO  - Synapse. 2005 Jan;55(1):45-51. doi: 10.1002/syn.20089.