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Titolo:
Noradrenaline provides long-term protection to dopaminergic neurons by reducing oxidative stress
Autore:
Troadec, JD; Marien, M; Darios, F; Hartmann, A; Ruberg, M; Colpaert, F; Michel, PP;
Indirizzi:
Hop La Pitie Salpetriere, INSERM, U289, F-75013 Paris, France Hop La PitieSalpetriere Paris France F-75013 289, F-75013 Paris, France Ctr Rech Pierre Fabre, F-81106 Castres, France Ctr Rech Pierre Fabre Castres France F-81106 re, F-81106 Castres, France
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 1, volume: 79, anno: 2001,
pagine: 200 - 210
SICI:
0022-3042(200110)79:1<200:NPLPTD>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOCUS-COERULEUS LESIONS; NERVE GROWTH-FACTOR; RAT-BRAIN; PARKINSONS-DISEASE; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; ISCHEMIC DAMAGE; CEREBRAL-CORTEX; CELL-DEATH; NEUROTRANSMITTERS;
Keywords:
catechol; dopamine neurons; neuroprotection; noradrenaline; oxidative stress;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Michel, PP Hop La Pitie Salpetriere, INSERM, U289, 47 Blvd Hop, F-75013 Paris, France Hop La Pitie Salpetriere 47 Blvd Hop Paris France F-75013 ance
Citazione:
J.D. Troadec et al., "Noradrenaline provides long-term protection to dopaminergic neurons by reducing oxidative stress", J NEUROCHEM, 79(1), 2001, pp. 200-210

Abstract

To better understand the neurotrophic function of the neurotransmitter noradrenaline, we have developed a model of mesencephalic cultures in which wefind low concentrations (0.3-10 muM) of noradrenaline to be remarkably effective in promoting long-term survival and function of dopaminergic neurons. This protective action reproduced the effect of caspase inhibition. It was atypical in that it occurred independently of adrenoceptor activation andwas mimicked by some antioxidants, redox metal chelators and the hydroxyl radical detoxifying enzyme catalase. Interestingly, intracellular reactive oxygen species (ROS) were drastically reduced by treatment with noradrenaline, indicating that the neurotransmitter itself acted as an antioxidant. Prevention of oxidative stress was, however, independent of the glutathione antioxidant defense system. Chemical analogues of noradrenaline bearing two free hydroxyl groups in the ortho position of the aromatic ring (o-catechols), as well as o-catechol itself, mimicked the survival promoting effects of the neurotransmitter, suggesting that this diphenolic structure was critical for both neuroprotection and reduction of ROS production. Paradoxically, the autoxidation of noradrenaline and the ensuing production of quinone metabolites may be required for both effects, as the neurotransmitter was spontaneously and rapidly degraded over time in the culture medium. These results support the concept that central noradrenergic mechanisms have a neuroprotective role, perhaps in part by reducing oxidative stress.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/10/20 alle ore 14:27:59