MPTP treatment increases expression of pre-pro-nociceptin/orphanin FQ mRNA in a subset of substantia nigra reticulata neurons

Neuroscience. 2010 Aug 11;169(1):269-78. doi: 10.1016/j.neuroscience.2010.04.033. Epub 2010 Apr 22.

Abstract

Antagonists selectively inhibiting activation of the nociceptin/orphanin FQ (N/OFQ) receptor reduce motor symptoms in experimental models of Parkinson's disease, and genetic deletion of the ppN/OFQ gene offers partial protection of mid-brain dopamine neurons against the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP increased ppN/OFQ mRNA expression in the substantia nigra (SN). We have evaluated the temporal relationship of dopamine cell loss to increased ppN/OFQ mRNA expression in the substantia nigra after MPTP treatment, and characterized the cellular locations in which increased ppN/OFQ mRNA expression was observed after MPTP treatment. MPTP increased by about 5-fold the number of neurons expressing ppN/OFQ mRNA in the pars reticulata of SN (SNr) by 24 h after treatment and the elevation remained significant for at least 7 days. This period coincided with the timing of the loss of dopamine neurons from the pars compacta of substantia nigra (SNc) after MPTP. The increased expression of ppN/OFQ mRNA co-localized with a neuronal marker in the SNr. MPTP treatment resulted in a small increase in the numbers of neurons expressing ppN/OFQ in the SNc in mice from one mouse colony but the increase did not reach statistical significance in mice from another colony. No changes in ppN/OFQ-mRNA expression were observed in the ventral tegmental area (VTA), the caudate-putamen, the subthalamic nucleus, or in two other brains areas. These results demonstrate that increased N/OFQ expression in the SNr is closely associated with the MPTP-induced loss of dopamine neurons in the SNc in a widely used animal model of Parkinson's disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Gene Expression Regulation / drug effects*
  • MPTP Poisoning / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / classification
  • Neurons / drug effects*
  • Neurons / metabolism
  • Opioid Peptides / biosynthesis
  • Opioid Peptides / genetics
  • Parkinsonian Disorders / genetics*
  • Protein Precursors / biosynthesis*
  • Protein Precursors / deficiency
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Receptors, Opioid / biosynthesis*
  • Receptors, Opioid / deficiency
  • Receptors, Opioid / genetics
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism

Substances

  • Opioid Peptides
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Opioid
  • prepronociceptin
  • nociceptin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine