PMID- 16749908
OWN - NLM
STAT- MEDLINE
DCOM- 20060818
LR  - 20131121
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 98
IP  - 2
DP  - 2006 Jul
TI  - Differential protection against MPTP or methamphetamine toxicity in dopamine 
      neurons by deletion of ppN/OFQ expression.
PG  - 495-505
AB  - Nociceptin (N/OFQ) is an endogenous neuropeptide that plays a role in the 
      behavioral deficits associated with Parkinson's disease (PD). The purpose of the 
      present study was to characterize the protective effects of prepro (pp)N/OFQ gene 
      deletion against two dopamine toxins, MPTP and methamphetamine (METH). Results 
      demonstrate that ppN/OFQ gene deletion attenuates the loss of both the number of 
      tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta 
      (SNpc) and loss of TH and vesicular monoamine transporter-2 (VMAT) 
      immunoreactivity in the caudate putamen (CPu) of MPTP-treated mice. This 
      protection was unaffected by age or gender, although, when loss of TH exceeded 
      90% in 5-6 month-old mice, the protective effect was greatly diminished. In 
      contrast, METH administration preferentially damaged dopaminergic terminals in 
      the CPu with little effect on dopamine neurons in the SNpc, an effect not 
      reversed by ppN/OFQ gene deletion. To determine if N/OFQ and MPP+ act directly 
      and synergistically on dopamine neurons, differentiated SH-SY5Y cells were 
      incubated with N/OFQ and/or MPP+. N/OFQ did not increase MPP+-mediated cell loss, 
      suggesting an indirect action of N/OFQ. These studies demonstrate that inhibition 
      of the endogenous N/OFQ system may represent a new therapeutic target for 
      prevention of neuronal loss associated with PD.
FAU - Brown, Jeffrey M
AU  - Brown JM
AD  - Department of Pharmacology, Uniformed Services University of the Health Sciences, 
      Bethesda, Maryland 20814, USA. jbrown@usuhs.mil
FAU - Gouty, Shawn
AU  - Gouty S
FAU - Iyer, Varsha
AU  - Iyer V
FAU - Rosenberger, John
AU  - Rosenberger J
FAU - Cox, Brian M
AU  - Cox BM
LA  - eng
GR  - DA003102/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060602
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Dopamine Agents)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, Opioid)
RN  - 0 (prepronociceptin)
RN  - 44RAL3456C (Methamphetamine)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*antagonists & inhibitors
MH  - Aging/physiology
MH  - Animals
MH  - Blotting, Western
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dopamine/*physiology
MH  - Dopamine Agents/*toxicity
MH  - Dopamine Uptake Inhibitors/*antagonists & inhibitors/*toxicity
MH  - Female
MH  - Gene Deletion
MH  - Image Processing, Computer-Assisted
MH  - Immunohistochemistry
MH  - Male
MH  - Methamphetamine/*antagonists & inhibitors/*toxicity
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*drug effects
MH  - Protein Precursors/genetics/*physiology
MH  - Receptors, Opioid/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Characteristics
EDAT- 2006/06/06 09:00
MHDA- 2006/08/19 09:00
CRDT- 2006/06/06 09:00
PHST- 2006/06/06 09:00 [pubmed]
PHST- 2006/08/19 09:00 [medline]
PHST- 2006/06/06 09:00 [entrez]
AID - JNC3902 [pii]
AID - 10.1111/j.1471-4159.2006.03902.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Jul;98(2):495-505. doi: 10.1111/j.1471-4159.2006.03902.x. Epub 
      2006 Jun 2.