Chronic stress alters the expression levels of longevity-related genes in the rat hippocampus.
The molecular mechanisms underlying the negative effects of psychological stress on cellular stress during aging and neurodegenerative diseases are poorly understood. The main objective of this study was to test the effect of chronic psychological stress, and the consequent increase of circulating glucocorticoids, on several hippocampal genes involved in longevity. Sirtuin-1, p53, thioredoxin-interacting protein, and heat shock protein 70 were studied at the mRNA and protein levels in stressed and non-stressed animals. Stress treatment for 10 days decreased sirtuin-1 and heat shock protein 70 levels, but increased levels of p53, thioredoxin-interacting protein and the NADPH oxidase enzyme. Examination of protein expression following two months of stress treatment indicated that sirtuin-1 remained depressed. In contrast, an increase was observed for thioredoxin-interacting protein, heat shock protein 70, p53 and the NADPH oxidase enzyme. The effect of stress was reversed by mifepristone, a glucocorticoid receptor antagonist. These data suggest that chronic stress could contribute to aging in the hippocampus.
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Ana C
AC
Sánchez-Hidalgo
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Mario F
MF
Muñoz
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Antonio J
AJ
Herrera
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Ana M
AM
Espinosa-Oliva
Department of Neuroscience, University of Rochester Medical Center, 601 Elmwood Avenue, Box 603, Rochester, NY 14642, USA.
Rianne
R
Stowell
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Antonio
A
Ayala
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Alberto
A
Machado
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
José L
JL
Venero
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain. Electronic address: depablos@us.es.
Rocío M
RM
de Pablos
D000818:Animals; D002908:Chronic Disease; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology
D056564:Sirtuin 1
Chronic stress; Glucocorticoids; Hippocampus; Oxidative stress; RU486; Sirtuins