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利血平诱导的大鼠帕金森病进展模型中的性别差异。

Sex differences in the progressive model of parkinsonism induced by reserpine in rats.

作者信息

Bispo José M M, Melo João E C, Gois Auderlan M, Leal Pollyana C, Lins Lívia C R F, Souza Marina F, Medeiros Katty A A L, Ribeiro Alessandra M, Silva Regina H, Marchioro Murilo, Santos José R

机构信息

Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil; Behavioral and Evolutionary Neurobiology Laboratory, Department of Biosciences, Federal University of Sergipe, Itabaiana, SE, Brazil.

Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.

出版信息

Behav Brain Res. 2019 May 2;363:23-29. doi: 10.1016/j.bbr.2019.01.041. Epub 2019 Jan 25.

DOI:10.1016/j.bbr.2019.01.041
PMID:30690108
Abstract

Parkinson's disease (PD) exhibits sexual differences in susceptibility and pathogenesis in humans, with a high incidence in men and a high severity of motor symptoms in male rodents. Furthermore, studies showed that the administration of low dose of reserpine (RES) induces a progressive appearance of motor alterations similar with parkinsonism in male rodents. Here, we investigated sex differences in motor deficits and tyrosine hydroxylase (TH) immunoreactivity induced by a progressive model of parkinsonism. Gonadally intact male and female Wistar rats and ovariectomized female rats received 15 subcutaneous injections (s.c.) every other day of 0.1 mg/kg of RES or vehicle. The repeated administration of low doses of RES (0.1 mg/kg) produces sexually dimorphic impairments on motor performance (catalepsy and open field test). Intact and ovariectomized females were more resistant to the deleterious effect of repeated administration of reserpine in the early, but this resistance in intact female disappears over time. However, intact females showed a reduction of the TH immunoreactivity in substantia nigra pars compacta, but not in ventral tegmental area and dorsal striatum. These results suggest a possible application of this model in the study of sexual dimorphism throughout the progression of PD.

摘要

帕金森病(PD)在人类的易感性和发病机制上存在性别差异,男性发病率高,雄性啮齿动物运动症状严重程度高。此外,研究表明,低剂量利血平(RES)给药会在雄性啮齿动物中诱导出与帕金森病相似的运动改变逐渐出现。在此,我们研究了帕金森病渐进模型诱导的运动缺陷和酪氨酸羟化酶(TH)免疫反应性的性别差异。性腺完整的雄性和雌性Wistar大鼠以及去卵巢雌性大鼠每隔一天皮下注射(s.c.)15次0.1mg/kg的RES或赋形剂。低剂量RES(0.1mg/kg)的重复给药对运动性能(僵住症和旷场试验)产生性别差异损伤。完整和去卵巢的雌性在早期对利血平重复给药的有害作用更具抵抗力,但完整雌性的这种抵抗力会随着时间消失。然而,完整雌性黑质致密部的TH免疫反应性降低,但腹侧被盖区和背侧纹状体未降低。这些结果表明该模型在PD进展过程中性别二态性研究中可能具有应用价值。

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