Kuter Katarzyna, Smiałowska Maria, Wierońska Joanna, Zieba Barbara, Wardas Jadwiga, Pietraszek Małgorzata, Nowak Przemysław, Biedka Izabela, Roczniak Wojciech, Konieczny Jolanta, Wolfarth Stanisław, Ossowska Krystyna
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Brain Res. 2007 Jun 25;1155:196-207. doi: 10.1016/j.brainres.2007.04.018. Epub 2007 Apr 12.
Paraquat is a toxin suggested to contribute to pathogenesis of Parkinson's disease. The aim of the present study was to examine toxic influence of subchronic treatment with this pesticide (5 days, one injection per day, 2-3 days of withdrawal) on dopaminergic, serotonergic, noradrenergic and GABAergic neurons. Paraquat decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra by 22% (measured 3 days after withdrawal). Two days after withdrawal the levels of the dopamine metabolites and dopamine turnover in the caudate-putamen, substantia nigra and prefrontal cortex were reduced by ca. 20-60%, and the binding of [(3)H]GBR 12,935 to dopamine transporter dropped by 25-40% in the caudate-putamen. Three days after paraquat withdrawal, the level of dopamine in the caudate-putamen was significantly increased, and earlier decreases in DOPAC and HVA in the substantia nigra, as well as [(3)H]GBR 12,935 binding in the caudate-putamen were reversed. Moreover, an increase in serotonin turnover in the caudate-putamen and prefrontal cortex, and noradrenaline level in the former structure was observed 2-3 days after paraquat withdrawal. Three days after the last paraquat injection 24-35% decreases in the proenkephalin mRNA levels and 5-7% reduction in glutamic acid decarboxylase (GAD)67 mRNA were found in the caudate-putamen. The present study suggests that subchronic paraquat administration triggers processes characteristic of early stages of dopaminergic neuron degeneration, and activates compensatory mechanisms involving dopaminergic, noradrenergic, serotonergic and GABAergic transmissions.
百草枯是一种被认为与帕金森病发病机制有关的毒素。本研究的目的是检测这种杀虫剂亚慢性治疗（5天，每天一次注射，停药2 - 3天）对多巴胺能、5-羟色胺能、去甲肾上腺素能和γ-氨基丁酸能神经元的毒性影响。百草枯使黑质中酪氨酸羟化酶免疫反应性（TH-ir）神经元数量减少了22%（停药3天后测量）。停药两天后，尾状核-壳核、黑质和前额叶皮质中多巴胺代谢产物水平和多巴胺周转率降低了约20 - 60%，并且尾状核-壳核中[(3)H]GBR 12,935与多巴胺转运体的结合下降了25 - 40%。百草枯停药三天后，尾状核-壳核中的多巴胺水平显著升高，黑质中DOPAC和HVA早期的降低以及尾状核-壳核中[(3)H]GBR 12,935结合的降低得以逆转。此外，百草枯停药2 - 3天后，观察到尾状核-壳核和前额叶皮质中5-羟色胺周转率增加，且前一结构中去甲肾上腺素水平升高。在最后一次注射百草枯三天后，尾状核-壳核中前脑啡肽原mRNA水平降低了24 - 35%，谷氨酸脱羧酶（GAD）67 mRNA降低了5 - 7%。本研究表明，亚慢性给予百草枯会引发多巴胺能神经元变性早期阶段的特征性过程，并激活涉及多巴胺能、去甲肾上腺素能、5-羟色胺能和γ-氨基丁酸能传递的代偿机制。
