title: Expression of peroxisome proliferator-activated receptor-gamma in the substantia nigra of hemiparkinsonian nonhuman primates.
abstract: OBJECTIVE
  To characterize the distribution of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the substantia nigra of normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated hemiparkinsonian monkeys, in order to validate PPAR-gamma as a target for neuroprotection.
  
  
  METHODS
  Immunohistochemical analysis of PPAR-gamma expression was performed in the substantia nigra and other select brain regions of fifteen rhesus monkeys including controls (n = 3), hemiparkinsonian necropsied after 3 (n = 5) or 12 (n = 3) months after MPTP, and animals who received MPTP+5 mg/kg of the PPAR-gamma agonist pioglitazone (n = 4).
  
  
  RESULTS
  PPAR-gamma expression was prominent in the subthalamic nucleus, oculomotor nucleus, ventral tegmental nucleus, and to a lesser extent, in the putamen; 3 or 12 months after MPTP, only the lesioned putamen had increased PPAR-gamma. Stereological cell quantification in normal subjects showed that approximately 50% of neurons in the substantia nigra pars compacta (SNpc) expressed PPAR-gamma. After MPTP, there was a significant loss of dopaminergic neurons in the ipsilateral SNpc and the actual numbers of tyrosine hydroxylase (TH) and PPAR-gamma cells were not significantly different at either time point. Pioglitazone dosing protected TH-positive neurons, closely matching the number of PPAR-gamma expressing cells in the ipsilateral SNpc. Nigral immunofluorescence verified colocalization of PPAR-gamma in neurons.
  
  
  CONCLUSIONS
  These results demonstrate that PPAR-gamma is expressed in the SNpc and putamen of nonhuman primates and, that the dopaminergic nigral neurons expressing PPAR-gamma are more likely to survive neurotoxin challenge after ligand activation by pioglitazone, therefore providing neuroanatomical validation for the use of PPAR-gamma agonists in Parkinson's disease (PD).
authors.forename: Christine
authors.initials: C
authors.lastname: Swanson
authors.forename: Marina
authors.initials: M
authors.lastname: Emborg
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002491:Central Nervous System Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010784:Photomicrography; D000077205:Pioglitazone; D011699:Putamen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000077205:Pioglitazone
keywords: Basal ganglia,; Inflammation,; MPTP,; Nonhuman primates,; PPAR-gamma,; Parkinson’s disease,; Pioglitazone,; Substantia nigra,; TH