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首页> 外文期刊>Frontiers in Aging Neuroscience >Testosterone Propionate Exacerbates the Deficits of Nigrostriatal Dopaminergic System and Downregulates Nrf2 Expression in Reserpine-Treated Aged Male Rats
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Testosterone Propionate Exacerbates the Deficits of Nigrostriatal Dopaminergic System and Downregulates Nrf2 Expression in Reserpine-Treated Aged Male Rats

机译：丙酸睾丸激素加重了利血平治疗的成年雄性大鼠的黑质纹状体多巴胺能系统的不足并下调了Nrf2表达。

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There is a controversy over the effects of testosterone supplements on dopaminergic function. Both neuroprotective and toxic effects of testosterone supplements are reported. The status of oxidative stress seems to explain the neuroprotective or toxic properties of testosterone. To determine the efficacy of testosterone supplements in different status of oxidative stress, the present studies analyzed the dopamine (DA)-related behaviors and neurochemical indices, as well as markers of nigrostriatal dopaminergic (NSDA) system in reserpine-treated aged male rats followed by testosterone propionate (TP) supplements. The status of oxidative stress of experimental animals was evaluated by analyzing oxidative stress parameters and nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway in substantia nigra (SN). Consistent with our previous studies, TP supplements to 21-month old aged male rats had the beneficial effects on NSDA system and DA-related behaviors and enhanced the antioxidative capabilities in SN. However, the beneficial effects of TP supplements on NSDA system and DA-related behaviors in aged male rats were reversed by reserpine pretreatment to them. Reserpine treatment induced the severe oxidative stress and reduced the expressions of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1) in the SN of aged male rats. The TP supplements to reserpine-pretreated aged male rats exacerbated the defects in NSDA system and DA-related behaviors, aggravated oxidative damages and downregulated the expression of Nrf2, HO-1 and NQO1 in the SN. These results suggested that the efficacy of TP supplements on impaired NSDA system was related to the status of oxidative stress in experimental rats.
机译：睾丸激素补充剂对多巴胺能功能的作用存在争议。睾丸激素补充剂具有神经保护作用和毒性作用。氧化应激的状态似乎可以解释睾丸激素的神经保护或毒性特性。为了确定睾丸激素补充剂在不同氧化应激状态下的功效，本研究分析了利血平治疗的雄性大鼠的多巴胺（DA）相关行为和神经化学指标，以及黑质纹状体多巴胺能（NSDA）系统的标志物，丙酸睾丸酮（TP）补充剂。通过分析黑质（SN）中的氧化应激参数和核因子红系2相关因子2（Nrf2）-抗氧化反应元件（ARE）信号传导途径来评估实验动物的氧化应激状态。与我们以前的研究一致，TP补充21月龄的雄性大鼠对NSDA系统和DA相关行为具有有益作用，并增强了SN中的抗氧化能力。然而，利血平预处理可逆转TP补充剂对老年雄性大鼠NSDA系统和DA相关行为的有益作用。利血平处理可导致老年雄性大鼠SN严重氧化应激并降低Nrf2，血红素氧合酶1（HO-1）和NAD（P）H：醌氧化还原酶1（NQO1）的表达。利血平预处理的成年雄性大鼠的TP补充剂加剧了NSDA系统和DA相关行为的缺陷，加剧了氧化损伤，并下调了SN中Nrf2，HO-1和NQO1的表达。这些结果表明，TP补充剂对受损NSDA系统的功效与实验大鼠的氧化应激状态有关。

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