title: MPTP animal model of Parkinsonism: dopamine cell death or only tyrosine hydroxylase impairment? A study using PET imaging, autoradiography, and immunohistochemistry in the cat.
abstract: OBJECTIVE
  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to produce experimental models of Parkinson's disease in laboratory animals. It is believed to cause a selective destruction of substantia nigra dopamine neurons, mainly based on a large reduction of tyrosine hydroxylase (TH), the catecholamine's synthesizing enzyme. Unlike Parkinson's disease in humans, however, all animal models are able to recover more or less rapidly from the MPTP induced Parkinsonian syndrome. This raises the question as whether MPTP causes a cell death with a decrease in dopamine transporter or a simple impairment of TH.
  
  
  METHODS
  To respond to this question, we quantified in a cat model of Parkinson's disease (MPTP 5 mg/kg i.p. during 5 days) the dopamine transporter using positron emission tomography (PET) imaging and autoradiography of [(11) C]PE2I and compared the data with the TH-immunoreactivity.
  
  
  RESULTS
  We found no changes in [(11) C]PE2I PET binding either 5 or 26 days after MPTP treatment when compared to baseline levels. Similarly, there were no significant changes in [(11) C]PE2I autoradiographic binding in the cat brain one week after MPTP treatment. In sharp contrast, MPTP treated cats exhibited severe Parkinson-like motor syndrome during the acute period with a marked decrease in TH-immunoreactivity in the striatum.
  
  
  CONCLUSIONS
  These data suggest that MPTP toxicity impairs efficiently TH and that such an effect is not necessarily accompanied by significant reduction of dopamine transporter seen with in vitro or in vivo [(11) C]PE2I binding.
authors.affiliation: CERMEP-Imaging Platform, Hospices Civils de Lyon, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Aznavour
authors.forename: Christophe
authors.initials: C
authors.lastname: Cendres-Bozzi
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lemoine
authors.forename: Colette
authors.initials: C
authors.lastname: Buda
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Sastre
authors.forename: Zoïa
authors.initials: Z
authors.lastname: Mincheva
authors.forename: Luc
authors.initials: L
authors.lastname: Zimmer
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001345:Autoradiography; D002415:Cats; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D020734:Parkinsonian Disorders / Q000201:enzymology* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine