Rudyk Chris, Litteljohn Darcy, Syed Shuaib, Dwyer Zach, Hayley Shawn
Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada.
Neurobiol Stress. 2015 Nov 12;2:85-93. doi: 10.1016/j.ynstr.2015.09.001. eCollection 2015.
A number of epidemiological and experimental studies have implicated the non-selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD). While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD). Hence, in the present study, we sought to take a multi-system approach to characterize the influence of paraquat upon extra-nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering neurochemical activity in the locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, dorsal striatum, and central amygdala. However, with the important exception striatal dopamine turnover, the stressor treatment did not further augment these effects. Additionally, paraquat altered inter-cytokine correlations and, to a lesser extent, circulating cytokine levels, and concomitant stress exposure modulated some of these effects. Finally, paraquat provoked significant (albeit modest) reductions of sucrose preference and weight gain, hinting at possible anhendonic-like or sickness responses. These data suggest that, in addition to being a well known oxidative stress generator, paraquat can act as a systemic stressor affecting hormonal and neurochemical activity, but largely not interacting with a concomitant stressor regimen.
多项流行病学和实验研究表明，非选择性除草剂百草枯与散发性帕金森病（PD）的发病有关。虽然临床前研究主要集中在阐明百草枯对黑质纹状体的影响，但关于非运动脑系统和炎症免疫过程（这些过程与PD有关）的数据相对较少。因此，在本研究中，我们试图采用多系统方法来描述百草枯对黑质纹状体以外脑区的影响，并确定在慢性间歇性应激源暴露的情况下，这种农药的影响是否会增强。我们的研究结果支持以下观点：百草枯本身作为一种全身性应激源，会增加血浆皮质酮水平，并改变蓝斑、下丘脑室旁核、伏隔核、背侧纹状体和中央杏仁核中的神经化学活性。然而，除了纹状体多巴胺周转率这一重要例外，应激源处理并没有进一步增强这些影响。此外，百草枯改变了细胞因子之间的相关性，并在较小程度上改变了循环细胞因子水平，同时应激暴露调节了其中一些影响。最后，百草枯引起蔗糖偏好和体重增加显著（尽管幅度较小）下降，暗示可能存在类似快感缺失或疾病的反应。这些数据表明，除了是一种众所周知的氧化应激产生剂外，百草枯还可以作为一种全身性应激源，影响激素和神经化学活性，但在很大程度上不与同时存在的应激源方案相互作用。
