title: Stress increases vulnerability to inflammation in the rat prefrontal cortex.
abstract: Inflammation could be involved in some neurodegenerative disorders that accompany signs of inflammation. However, because sensitivity to inflammation is not equal in all brain structures, a direct relationship is not clear. Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 microg of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-alpha; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11beta-[p-(dimethylamino)phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.
authors.affiliation: Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: de Pablos
authors.forename: R F
authors.initials: RF
authors.lastname: Villarán
authors.forename: S
authors.initials: S
authors.lastname: Argüelles
authors.forename: A J
authors.initials: AJ
authors.lastname: Herrera
authors.forename: J L
authors.initials: JL
authors.lastname: Venero
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: J
authors.initials: J
authors.lastname: Cano
authors.forename: A
authors.initials: A
authors.lastname: Machado
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017397:Prefrontal Cortex; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins