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Titolo:
Lack of tissue glucocorticoid reactivation in 11 beta-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments
Autore:
Yau, JLW; Noble, J; Kenyon, CJ; Hibberd, C; Kotelevtsev, Y; Mullins, JJ; Seckl, JR;
Indirizzi:
Univ Edinburgh, Western Gen Hosp, Ctr Study Aging Brain, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH4 2XU Midlothian, Scotland Univ Edinburgh, Edinburgh EH8 9AG, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH8 9AG Midlothian, Scotland
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 8, volume: 98, anno: 2001,
pagine: 4716 - 4721
SICI:
0027-8424(20010410)98:8<4716:LOTGRI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR ACTIVATION; GENE-EXPRESSION; CORTISOL-LEVELS; SPATIAL MEMORY; HIPPOCAMPUS; RAT; LOCALIZATION; CORTICOSTERONE; POTENTIATION; PERFORMANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Yau, JLW Univ Edinburgh, Western Gen Hosp, Ctr Study Aging Brain, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH4 2XU n, Scotland
Citazione:
J.L.W. Yau et al., "Lack of tissue glucocorticoid reactivation in 11 beta-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments", P NAS US, 98(8), 2001, pp. 4716-4721

Abstract

11 beta -hydroxysteroid dehydrogenase type 1 (11 beta -HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11 beta -HSD-1 acts as a functional 11 beta -reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11beta -HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlatedwith learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11 beta -HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of localenzymes in determining intracellular glucocorticoid activity. Selective 11beta -HSD-1 inhibitors may protect against hippocampal function decline with age.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 04:34:36