Early post-treatment with 9-cis retinoic acid reduces neurodegeneration of dopaminergic neurons in a rat model of Parkinson’s disease

BMC Neuroscience

Research Article

Cristina M Bäckman¹  Oscar Diaz-Ruiz¹  Seong-Jin Yu²  Eunkyung Bae²  Yun Wang²  Hui Shen²  Lian-Hu Yin³ 

[1] Integrative Neuroscience Section, National Institute on Drug Abuse, IRP, Baltimore, MD, USA;Neural Protection and Regeneration Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA;Neural Protection and Regeneration Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA;Department of Neurosurgery, Luhe Teaching Hospital, Capital Medical University, Beijing, China;

关键词: Retinoic Acid;    Tyrosine Hydroxylase;    Middle Cerebral Artery Occlusion;    Rotational Behavior;    Ventral Mesencephalon;   

DOI  :  10.1186/1471-2202-13-120

 received in 2012-06-01, accepted in 2012-10-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundRetinoic 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).ResultsThe 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.ConclusionOur data suggests that early post-treatment with 9cRA has a protective effect against neurodegeneration in nigrostriatal DA neurons in an animal model of PD.

【 授权许可】

Unknown   
© Yin et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.