title: Early post-treatment with 9-cis retinoic acid reduces neurodegeneration of dopaminergic neurons in a rat model of Parkinson's disease.
abstract: BACKGROUND
  Retinoic acid (RA) is a biologically active derivative of vitamin A. Previous studies have demonstrated that RA has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. Pretreatment with 9-cis-retinoic acid (9cRA) reduced infarction and TUNEL labeling in cerebral cortex as well as attenuated neurological deficits after distal middle cerebral artery occlusion in rats. The purpose of this study was to examine a protective role of 9cRA in dopaminergic (DA) neurons in a typical rodent model of Parkinson's disease (PD).
  
  
  RESULTS
  The protective role of 9cRA was first examined in rat primary ventromesencephalic culture. Treatment with 9cRA significantly reduced 6-hydroxydopamine (6-OHDA)-mediated cell death and TUNEL labeling in cultured dopaminergic neurons. The protective effect was also examined in adult male rats. Animals received unilateral 6-OHDA lesioning at the left medial forebrain bundle on day 0. Methamphetamine -induced rotational behavior was examined on days 6, 20 and 30 after lesioning. Animals were separated into 2 groups to balance rotational behavior and lesion extent on day 6 and were treated with either 9cRA or vehicle (i.c.v. on day 7 + intra-nasal from day 8 to day 14). Post-treatment with 9cRA significantly reduced methamphetamine -mediated ipislateral rotation at 20 and 30 days after lesioning. In vivo voltammetry was used to examine DA overflow in striatum. Treatment with 9cRA significantly increased KCl -evoked DA release in the lesioned striatum. 9cRA also increased tyrosine hydroxylase (+) cell number in the lesioned nigra as determined by unbiased stereology.
  
  
  CONCLUSIONS
  Our data suggests that early post-treatment with 9cRA has a protective effect against neurodegeneration in nigrostriatal DA neurons in an animal model of PD.
authors.affiliation: Neural Protection and Regeneration Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
authors.forename: Lian-Hu
authors.initials: LH
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Oscar
authors.initials: O
authors.lastname: Diaz-Ruiz
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Bäckman
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Bae
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Yu
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D007839:Functional Laterality; D020287:In Situ Nick-End Labeling; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology / Q000473:pathology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014212:Tretinoin / Q000627:therapeutic use*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D014212:Tretinoin; D011189:Potassium Chloride; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase