title: Chronic stress enhances microglia activation and exacerbates death of nigral dopaminergic neurons under conditions of inflammation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, E-41012 Seville, Spain. depablos@us.es.
authors.forename: Rocío M
authors.initials: RM
authors.lastname: de Pablos
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Herrera
authors.forename: Ana M
authors.initials: AM
authors.lastname: Espinosa-Oliva
authors.forename: Manuel
authors.initials: M
authors.lastname: Sarmiento
authors.forename: Mario F
authors.initials: MF
authors.lastname: Muñoz
authors.forename: Alberto
authors.initials: A
authors.lastname: Machado
authors.forename: José L
authors.initials: JL
authors.lastname: Venero
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011134:Polysaccharides; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008054:Lipid Peroxides; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D052247:Nitric Oxide Synthase Type II; D003345:Corticosterone