Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
Neurotox Res. 2011 Jan;19(1):162-71. doi: 10.1007/s12640-010-9153-7. Epub 2010 Feb 9.
Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing is known about the role of glycogen synthase kinase-3β (GSK-3β) in the PQ toxicity. Therefore, the aim of this study was to examine the influence of 37-week administration of PQ in rats on the immunohistochemically measured levels of the total GSK-3β and its active, tyrosine 216 (pY216)-phosphorylated form in subcellular fractions of the midbrain with pons, as well as of the striatum. The present results revealed that the long-term PQ administration increased the levels of total and active forms of GSK-3β in the midbrain with pons, whereas decreased them in the striatum. Examination of the lesion extent showed a decrease in the number of tyrosine-immunoreactive neurons in the substantia nigra pars compacta, ventral tegmental area, and locus coeruleus, as well as lower DOPAC/dopamine ratio and noradrenaline level in the striatum in rats treated with PQ. The long-term PQ administration disturbed also motor activity of rats. Summarizing, the present data indicate that the long-term exposure of rats to PQ, a commonly used herbicide, diversely alters levels of GSK-3β in different brain structures, which may be associated with their vulnerability to its toxicity.
帕金森病是一种进展缓慢的疾病，由于黑质中的多巴胺能神经元病变和纹状体中多巴胺的急剧丧失。现在人们认为，几种环境因素，包括除草剂百草枯（PQ），可能有助于其发病机制。然而，到目前为止，还没有人知道糖原合酶激酶-3β（GSK-3β）在 PQ 毒性中的作用。因此，本研究的目的是研究 37 周 PQ 给药对大鼠中脑桥部和纹状体亚细胞部分中总 GSK-3β及其活性形式酪氨酸 216（pY216）磷酸化形式的免疫组织化学测量水平的影响。目前的结果表明，长期 PQ 给药增加了中脑桥部总 GSK-3β和活性 GSK-3β的水平，而降低了纹状体中的水平。对病变程度的检查显示，PQ 处理大鼠的黑质致密部、腹侧被盖区和蓝斑中的酪氨酸免疫反应性神经元数量减少，纹状体中的 DOPAC/多巴胺比值和去甲肾上腺素水平降低。长期 PQ 给药还扰乱了大鼠的运动活动。综上所述，本数据表明，大鼠长期暴露于百草枯（一种常用的除草剂）会在不同的大脑结构中不同地改变 GSK-3β的水平，这可能与其对其毒性的易感性有关。
