Bassani Taysa B, Gradowski Raisa W, Zaminelli Tiago, Barbiero Janaína K, Santiago Ronise M, Boschen Suelen L, da Cunha Claudio, Lima Marcelo M S, Andreatini Roberto, Vital Maria A B F
Pharmacology Department, Federal University of Paraná, Brazil.
Physiology Department, Federal University of Paraná, Brazil.
Brain Res. 2014 Dec 17;1593:95-105. doi: 10.1016/j.brainres.2014.09.068. Epub 2014 Oct 6.
Parkinson׳s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Systemic and intranigral exposure to rotenone in rodents reproduces many of the pathological and behavioral features of PD in humans and thus has been used as an animal model of the disease. Melatonin is a neurohormone secreted by the pineal gland, which has several important physiological functions. It has been reported to be neuroprotective in some animal models of PD. The present study investigated the effects of prolonged melatonin treatment in rats previously exposed to rotenone. The animals were intraperitoneally treated for 10 days with rotenone (2.5mg/kg) or its vehicle. 24h later, they were intraperitoneally treated with melatonin (10mg/kg) or its vehicle for 28 days. One day after the last rotenone exposure, the animals exhibited hypolocomotion in the open field test, which spontaneously reversed at the last motor evaluation. We verified that prolonged melatonin treatment after dopaminergic lesion did not alter motor function but produced antidepressant-like effects in the forced swim test, prevented the rotenone-induced reduction of striatal dopamine, and partially prevented tyrosine hydroxylase immunoreactivity loss in the SNpc. Our results indicate that melatonin exerts neuroprotective and antidepressant-like effects in the rotenone model of PD.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质致密部（SNpc）中的多巴胺能神经元逐渐丧失。啮齿动物全身和黑质内暴露于鱼藤酮会重现人类PD的许多病理和行为特征，因此已被用作该疾病的动物模型。褪黑素是松果体分泌的一种神经激素，具有多种重要的生理功能。据报道，它在一些PD动物模型中具有神经保护作用。本研究调查了长期给予褪黑素对先前暴露于鱼藤酮的大鼠的影响。动物腹腔注射鱼藤酮（2.5mg/kg）或其溶剂10天。24小时后，它们腹腔注射褪黑素（10mg/kg）或其溶剂，持续28天。在最后一次暴露于鱼藤酮一天后，动物在旷场试验中表现出运动减少，在最后一次运动评估时自发恢复。我们证实，多巴胺能损伤后长期给予褪黑素不会改变运动功能，但在强迫游泳试验中产生了类似抗抑郁的作用，防止了鱼藤酮诱导的纹状体多巴胺减少，并部分防止了SNpc中酪氨酸羟化酶免疫反应性的丧失。我们的结果表明，褪黑素在PD的鱼藤酮模型中发挥神经保护和类似抗抑郁的作用。
