Neural Protection and Regeneration Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
BMC Neurosci. 2012 Oct 6;13:120. doi: 10.1186/1471-2202-13-120.
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).
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.
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.
维甲酸（RA）是维生素 A 的生物活性衍生物。先前的研究表明，RA 对系膜细胞和 PC12 细胞中由 H2O2 或氧葡萄糖剥夺引起的损伤具有保护作用。9-顺维甲酸（9cRA）预处理可减少大鼠大脑皮质中的梗死和 TUNEL 标记，并减轻大脑中动脉远端闭塞后的神经功能缺损。本研究旨在研究 9cRA 在典型帕金森病（PD）啮齿动物模型中对多巴胺能（DA）神经元的保护作用。
首先在大鼠原代脑室下培养物中检查了 9cRA 的保护作用。9cRA 处理可显著降低 6-羟多巴胺（6-OHDA）介导的培养多巴胺能神经元的细胞死亡和 TUNEL 标记。还在成年雄性大鼠中检查了保护作用。动物在第 0 天接受左侧内侧前脑束单侧 6-OHDA 损伤。在损伤后第 6、20 和 30 天检查安非他命诱导的旋转行为。动物在第 6 天分为 2 组，以平衡旋转行为和损伤程度，并在第 7 天用 9cRA 或载体（侧脑室注射，第 8 天至第 14 天鼻内给药）治疗。损伤后用 9cRA 治疗可显著减少损伤后 20 和 30 天安非他命介导的 ipsilateral 旋转。使用体内伏安法检查纹状体中 DA 的溢出。9cRA 处理可显著增加损伤纹状体中 KCl 诱导的 DA 释放。9cRA 还通过无偏立体学增加损伤黑质中酪氨酸羟化酶（+）细胞数量。
我们的数据表明，9cRA 早期治疗对 PD 动物模型中黑质纹状体 DA 神经元的神经退行性变具有保护作用。
