| Greater resistance to inflammation at adulthood could contribute to extended life span of p66(Shc-/-) mice. | |
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MedLine Citation:
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PMID: 20085805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Evidence is mounting that reactive oxygen species (ROS) produced because of stressful challenges could interfere with the proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in greater vulnerability to aging and neurodegeneration. Here we tested the hypothesis that p66(Shc-/-) mice, which have been described to have an extended life span and a high resistance to oxidative stress, might be less susceptible to the effects of inflammatory insults at adulthood. Although adrenocortical reactivity in response to bacterial endotoxin (lipopolysaccharide, LPS) did not differ as a function of the genotype, a hyperdrive of the HPA axis was revealed following treatment with a synthetic glucocorticoid agonist. When measuring changes in hippocampal oxidative status following LPS, only wild-type (WT) subjects showed increased levels of F(2)-isoprostanes, an index of lipid peroxidation and free radical formation. At the same time, the neurotrophin brain-derived neurotrophic factor was selectively increased in WT subjects, while levels of prostaglandin E(2) were decreased in the mutants. Overall, the greater resilience to inflammation-induced changes in the p66(Shc-/-) mutants might underlie the better health status and the longevity characterizing these mice. |
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Authors:
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Alessandra Berry; Daniela Carnevale; Marco Giorgio; Pier Giuseppe Pelicci; Edo Ronald de Kloet; Enrico Alleva; Luisa Minghetti; Francesca Cirulli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-18 |
Journal Detail:
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Title: Experimental gerontology Volume: 45 ISSN: 1873-6815 ISO Abbreviation: Exp. Gerontol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-12 Completed Date: 2010-07-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047061 Medline TA: Exp Gerontol Country: England |
Other Details:
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Languages: eng Pagination: 343-50 Citation Subset: IM |
Affiliation:
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Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain-Derived Neurotrophic Factor / analysis Corticosterone / blood Dexamethasone / pharmacology Dinoprost / analogs & derivatives, analysis Dinoprostone / analysis Inflammation / prevention & control* Lipopolysaccharides / pharmacology Longevity* Male Mice Mice, Knockout Oxidative Stress Shc Signaling Adaptor Proteins / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Brain-Derived Neurotrophic Factor; 0/Lipopolysaccharides; 0/Shc Signaling Adaptor Proteins; 0/Shc1 protein, mouse; 27415-26-5/8-epi-prostaglandin F2alpha; 363-24-6/Dinoprostone; 50-02-2/Dexamethasone; 50-22-6/Corticosterone; 551-11-1/Dinoprost |
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