Chronic stress enhances microglia activation and exacerbates death of nigral dopaminergic neurons under conditions of inflammation

Journal of Neuroinflammation

José L Venero¹  Alberto Machado¹  Mario F Muñoz¹  Manuel Sarmiento²  Ana M Espinosa-Oliva¹  Antonio J Herrera¹  Rocío M de Pablos¹ 

[1] Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, E-41013 Seville, Spain;Present address: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford OX3 7LJ, UK

关键词: Substantia nigra;    Stress;    Parkinson’s disease;    Microglia;    Lipopolysaccharide;    Glucocorticoids;   

Others  :  824147
DOI  :  10.1186/1742-2094-11-34

 received in 2013-10-23, accepted in 2014-02-07,  发布年份 2014

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 de Pablos et al.; licensee BioMed Central Ltd.

【 图 表 】

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