Urbanavicius Jessika, Ferreira Margot, Costa Gustavo, Abin-Carriquiry Juan Andrés, Wonnacott Susan, Dajas Federico
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
J Neurochem. 2007 Aug;102(3):723-30. doi: 10.1111/j.1471-4159.2007.04560.x. Epub 2007 Apr 16.
It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) in this experimental paradigm, we have examined its activity by assessing the accumulation of l-3,4-dihydroxyphenylalanine after inhibiting the subsequent enzyme in the DA synthetic pathway, aromatic l-amino acid decarboxylase, with 3-hydroxybenzylhydrazine. In addition the amount of TH protein was assessed by western blotting and its distribution in the CS was examined using immunohistochemical methods. 6-hydroxydopamine injection produced a significant decrease in DA levels and l-3,4-dihydroxyphenylalanine accumulation, as well as decreases in TH protein and TH immunoreactive fibres in the CS. After nicotine treatment, the decrease in TH protein in the CS was significantly reduced, with a concomitant preservation of TH activity, but nicotine did not alter the number of TH immunoreactive fibres. The activity and amount of TH did not change in the contralateral (intact) CS. Thus, nicotine induces long lasting TH plasticity in the degenerating CS. A synergistic action of nicotine-activated and lesion-originated signals appears necessary for the expression of this neuronal molecular plasticity.
已表明，在黑质注射6-羟基多巴胺后，尼古丁可防止纹状体中多巴胺（DA）的丢失。为了研究酪氨酸羟化酶（TH；EC 1.14.16.2）在该实验范式中的作用，我们通过用3-羟基苄基肼抑制DA合成途径中的后续酶芳香族L-氨基酸脱羧酶后，评估L-3,4-二羟基苯丙氨酸的积累来检测其活性。此外，通过蛋白质印迹法评估TH蛋白的量，并使用免疫组织化学方法检查其在纹状体中的分布。注射6-羟基多巴胺导致DA水平和L-3,4-二羟基苯丙氨酸积累显著降低，以及纹状体中TH蛋白和TH免疫反应性纤维减少。尼古丁处理后，纹状体中TH蛋白的减少显著减轻，同时TH活性得以保留，但尼古丁并未改变TH免疫反应性纤维的数量。对侧（完整）纹状体中TH的活性和量没有变化。因此，尼古丁在退化的纹状体中诱导持久的TH可塑性。尼古丁激活信号和损伤起源信号的协同作用似乎是这种神经元分子可塑性表达所必需的。
