Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Wattana, Bangkok, Thailand.
J Pineal Res. 2012 Jan;52(1):128-37. doi: 10.1111/j.1600-079X.2011.00927.x. Epub 2011 Aug 18.
Alpha-synuclein (α-syn) is a neuronal protein that is involved in various degenerative disorders such as Parkinson's disease. It is found in the presynaptic terminals and perinuclear zones of many brain regions. Amphetamine (AMPH), a psychostimulant drug abused progressively more commonly in recent years, has been known to induce neurotoxicity in the central dopaminergic pathway, which is associated with increased oxidative stress. Recently, AMPH has been shown to significantly increase the level of α-syn in dopaminergic neuroblastoma cell cultures. Melatonin is recognized as an antioxidant for the nervous system. This study tested whether melatonin can attenuate the effect of AMPH on the expression of α-syn in the dopaminergic pathway of the neonatal rat. Four-day old postnatal rats (P4) were injected subcutaneously with either AMPH (increasing dose, 5-10 mg/kg daily) alone or AMPH with melatonin (2 mg/kg) daily at 10:00 AM for 7 consecutive days. As determined using Western blot, the level of α-syn was significantly increased in the substantia nigra, dorsal striatum, nucleus accumbens, and prefrontal cortex of the AMPH-treated group, while melatonin treatment either prior to AMPH or alone decreased the accumulation of the protein to 77%, 96%, 78%, and 77% of the control value, respectively. Furthermore, an immunofluorescent study showed that the α-syn-immunoreactivity increased noticeably in the nuclei of cell bodies and nerve terminals of the AMPH-treated group. Again, melatonin lowered this immunoreactivity. These results indicate that melatonin has a direct or indirect effect in reducing the expression of α-syn in the postnatal rat. The exact mechanism of this mitigation should be further investigated.
α-突触核蛋白（α-syn）是一种参与多种退行性疾病的神经元蛋白，如帕金森病。它存在于许多脑区的突触前末梢和核周区。安非他命（AMPH），一种近年来越来越被滥用的精神兴奋剂药物，已知会在中枢多巴胺能通路中诱导神经毒性，这与氧化应激增加有关。最近，AMPH 已被证明可显著增加多巴胺能神经母细胞瘤细胞培养物中α-syn 的水平。褪黑素被认为是神经系统的抗氧化剂。本研究测试了褪黑素是否能减弱 AMPH 对新生大鼠多巴胺能通路中α-syn 表达的影响。新生后 4 天（P4）的大鼠（P4）每天上午 10 点皮下注射 AMPH（递增剂量，5-10mg/kg），或 AMPH 加褪黑素（2mg/kg），连续 7 天。如通过 Western blot 测定，α-syn 的水平在 AMPH 处理组的黑质、背侧纹状体、伏隔核和前额叶皮质中显著增加，而褪黑素在 AMPH 之前或单独处理可使该蛋白的积累分别降低至对照值的 77%、96%、78%和 77%。此外，免疫荧光研究显示，α-syn-免疫反应性在 AMPH 处理组的细胞体和神经末梢的核中明显增加。同样，褪黑素降低了这种免疫反应性。这些结果表明，褪黑素在降低新生大鼠中α-syn 的表达方面具有直接或间接的作用。这种缓解的确切机制应进一步研究。
