Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, E-41012 Seville, Spain.
J Neuroinflammation. 2014 Feb 24;11:34. doi: 10.1186/1742-2094-11-34.
Parkinson's disease is an irreversible neurodegenerative disease linked to progressive movement disorders and is accompanied by an inflammatory reaction that is believed to contribute to its pathogenesis. Since sensitivity to inflammation is not the same in all brain structures, the aim of this work was to test whether physiological conditions as stress could enhance susceptibility to inflammation in the substantia nigra, where death of dopaminergic neurons takes place in Parkinson's disease.
To achieve our aim, we induced an inflammatory process in nonstressed and stressed rats (subject to a chronic variate stress) by a single intranigral injection of lipopolysaccharide, a potent proinflammogen. The effect of this treatment was evaluated on inflammatory markers as well as on neuronal and glial populations.
Data showed a synergistic effect between inflammation and stress, thus resulting in higher microglial activation and expression of proinflammatory markers. More important, the higher inflammatory response seen in stressed animals was associated with a higher rate of death of dopaminergic neurons in the substantia nigra, the most characteristic feature seen in Parkinson's disease. This effect was dependent on glucocorticoids.
Our data demonstrate that stress sensitises midbrain microglia to further inflammatory stimulus. This suggests that stress may be an important risk factor in the degenerative processes and symptoms of Parkinson's disease.
帕金森病是一种不可逆的神经退行性疾病，与进行性运动障碍有关，并伴有炎症反应，据信这有助于其发病机制。由于所有脑结构对炎症的敏感性并不相同，因此本研究的目的是测试生理条件（如应激）是否会增加帕金森病中多巴胺能神经元死亡的黑质对炎症的易感性。
为了达到我们的目的，我们通过向黑质内单次注射脂多糖（一种有效的促炎原），在非应激和应激大鼠（接受慢性变异性应激）中诱导炎症过程。评估这种治疗对炎症标志物以及神经元和神经胶质群体的影响。
数据显示炎症和应激之间存在协同作用，从而导致小胶质细胞的激活和促炎标志物的表达增加。更重要的是，应激动物中观察到的更高炎症反应与黑质中多巴胺能神经元更高的死亡率有关，这是帕金森病最典型的特征。这种作用依赖于糖皮质激素。
我们的数据表明，应激使中脑小胶质细胞对进一步的炎症刺激敏感。这表明应激可能是帕金森病退行性过程和症状的一个重要危险因素。
