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Glucocorticoids are potent regulators of the innate immune response, and alteration in this inhibitory feedback has detrimental consequences for the neural tissue. This study profiled and investigated functionally candidate genes mediating this switch between cell survival and death during an acute inflammatory reaction subsequent to the absence of glucocorticoid signaling. Oligonucleotide microarray analysis revealed that following lipopolysaccharide (LPS) intracerebral administration at striatum level, more modulated genes presented transcription impairment than exacerbation upon glucocorticoid receptor blockage. Among impaired genes we identified ceruloplasmin (Cp), which plays a key role in iron metabolism and is implicated in a neurodegenative disease. Microglial and endothelial induction of Cp is a natural neuroprotective mechanism during inflammation, because Cp-deficient mice exhibited increased iron accumulation and demyelination when exposed to LPS and neurovascular reactivity to pneumococcal meningitis. This study has identified genes that can play a critical role in programming the innate immune response, helping to clarify the mechanisms leading to protection or damage during inflammatory conditions in the CNS. © 2007 Glezer et al.


Documento: Artículo
Título:Genes involved in the balance between neuronal survival and death during inflammation
Autor:Glezer, I.; Chernomoretz, A.; David, S.; Plante, M.-M.; Rivest, S.
Filiación:Laboratory of Molecular Endocrinology, Centre Hospitalier de l'Université Laval (CHUL), Research Center and Department of Anatomy and Physiology, Laurier, QC, Canada
Physics Department, FCEyN, University of Buenos Aires, Buenos Aires, Argentina
Center for Research in Neuroscience, Research Institute of the McGill University Health Center, Montreal General Hospital Research Institute, Montreal, QC, Canada
Palabras clave:ceruloplasmin; glucocorticoid; glucocorticoid receptor; lipopolysaccharide; oligonucleotide; ceruloplasmin; glucocorticoid; iron; lipopolysaccharide; animal cell; animal experiment; animal model; article; bacterial meningitis; cell survival; central nervous system disease; controlled study; corpus striatum; degenerative disease; demyelination; endothelium; gene expression regulation; gene function; gene identification; genetic transcription; immunopathogenesis; innate immunity; iron metabolism; microarray analysis; microglia; molecular mechanics; mouse; nerve cell necrosis; neurodegeneration with brain iron accumulation; neuroprotection; nonhuman; receptor blocking; signal transduction; animal; cell survival; chemically induced disorder; demyelinating disease; DNA microarray; genetics; inflammation; metabolism; methodology; mouse mutant; nerve cell; pathology; Mus; Animals; Cell Survival; Ceruloplasmin; Demyelinating Diseases; Glucocorticoids; Inflammation; Iron; Lipopolysaccharides; Mice; Mice, Knockout; Microarray Analysis; Neurons; Oligonucleotide Array Sequence Analysis
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
CAS:ceruloplasmin, 9031-37-2; iron, 14093-02-8, 53858-86-9, 7439-89-6; Ceruloplasmin,; Glucocorticoids; Iron, 7439-89-6; Lipopolysaccharides


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---------- APA ----------
Glezer, I., Chernomoretz, A., David, S., Plante, M.-M. & Rivest, S. (2007) . Genes involved in the balance between neuronal survival and death during inflammation. PLoS ONE, 2(3).
---------- CHICAGO ----------
Glezer, I., Chernomoretz, A., David, S., Plante, M.-M., Rivest, S. "Genes involved in the balance between neuronal survival and death during inflammation" . PLoS ONE 2, no. 3 (2007).
---------- MLA ----------
Glezer, I., Chernomoretz, A., David, S., Plante, M.-M., Rivest, S. "Genes involved in the balance between neuronal survival and death during inflammation" . PLoS ONE, vol. 2, no. 3, 2007.
---------- VANCOUVER ----------
Glezer, I., Chernomoretz, A., David, S., Plante, M.-M., Rivest, S. Genes involved in the balance between neuronal survival and death during inflammation. PLoS ONE. 2007;2(3).