Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure
Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure
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DOI：
10.1007/s11064-018-2477-z
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发表时间：
2018-03-01
影响因子：
4.4
通讯作者：
Farina, Marcelo
中科院分区：
文献类型：
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作者：
Goncalves, CinaraLudvig;dos Santos, Danubia Bonfanti;Farina, Marcelo
在动物模型中，脂多糖（LPS）引起的全身炎症破坏了血脑屏障（BBB）的稳态。这一事件导致几种脑结构对血液中存在的潜在神经毒物的易感性增加。在本研究中，我们研究了交替腹腔注射LPS对治疗后24 h和60 d纹状体血脑屏障通透性、社会识别记忆和生化参数的影响。此外，我们还研究了暴露于中等神经毒性剂量的除草剂百草枯是否会增强lps诱导的神经毒性。脂多糖处理引起血脑屏障完整性的短暂破坏，这可以通过纹状体中外源性荧光素钠水平的增加来证明。此外，LPS暴露导致社会识别记忆的延迟损伤（治疗后第38天评估）和纹状体3-硝基酪氨酸水平的增加。这些事件是在纹状体和黑质中运动协调性和酪氨酸羟化酶（TH）水平没有显著变化的情况下观察到的。PQ暴露导致纹状体线粒体复合体I活性长期下降，但并未改变lps诱导的行为和纹状体生化变化。结果表明，全身给药LPS会导致成年小鼠延迟的社会识别、记忆缺陷和纹状体亚硝化应激，而中等毒性剂量的PQ并没有放大这些事件。此外，PQ诱导的纹状体线粒体复合体I的抑制也未被LPS放大，表明LPS和PQ在该实验模型中不存在协同神经毒性作用。
Systemic inflammation triggered by lipopolysaccharide (LPS) administration disrupts blood-brain barrier (BBB) homeostasis in animal models. This event leads to increased susceptibility of several encephalic structures to potential neurotoxicants present in the bloodstream. In this study, we investigated the effects of alternate intraperitoneal injections of LPS on BBB permeability, social recognition memory and biochemical parameters in the striatum 24 h and 60 days after treatments. In addition, we investigated whether the exposure to a moderate neurotoxic dose of the herbicide paraquat could potentiate LPS-induced neurotoxicity. LPS administration caused a transient disruption of BBB integrity, evidenced by increased levels of exogenously administered sodium fluorescein in the striatum. Also, LPS exposure caused delayed impairment in social recognition memory (evaluated at day 38 after treatments) and increase in the striatal levels of 3-nitrotyrosine. These events were observed in the absence of significant changes in motor coordination and in the levels of tyrosine hydroxylase (TH) in the striatum and substantia nigra. PQ exposure, which caused a long-lasting decrease of striatal mitochondrial complex I activity, did not modify LPS-induced behavioral and striatal biochemical changes. The results indicate that systemic administration of LPS causes delayed social recognition memory deficit and striatal nitrosative stress in adult mice and that the coexposure to a moderately toxic dose of PQ did not magnify these events. In addition, PQ-induced inhibition of striatal mitochondrial complex I was also not magnified by LPS exposure, indicating the absence of synergic neurotoxic effects of LPS and PQ in this experimental model.