Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase
Autore:
Hogema, BM; Gupta, M; Senephansiri, H; Burlingame, TG; Taylor, M; Jakobs, C; Schutgens, RBH; Froestl, W; Snead, OC; Diaz-Arrastia, R; Bottiglieri, T; Grompe, M; Gibson, KM;
Indirizzi:
Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 Genet, Portland, OR 97201 USA Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metab Unit, Amsterdam, Netherlands Vrije Univ Amsterdam Amsterdam Netherlands Unit, Amsterdam, Netherlands Erasmus Univ, Fac Med, Cardiovasc Res Inst COEUR, Dept Biochem, NL-3000 DRRotterdam, Netherlands Erasmus Univ Rotterdam Netherlands NL-3000 DR 0 DRRotterdam, Netherlands Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 Pediat, Portland, OR 97201 USA Novartis Pharma Inc, CH-4002 Basel, Switzerland Novartis Pharma Inc Basel Switzerland CH-4002 CH-4002 Basel, Switzerland Hosp Sick Children, Fac Med, Dept Pediat, Div Neurol, Toronto, ON, Canada Hosp Sick Children Toronto ON Canada at, Div Neurol, Toronto, ON, Canada Hosp Sick Children, Fac Med, Program Brain & Behav, Toronto, ON, Canada Hosp Sick Children Toronto ON Canada Brain & Behav, Toronto, ON, Canada Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75235 USA Univ Texas Dallas TX USA 75235 Med Ctr, Dept Neurol, Dallas, TX 75235 USA Baylor Univ, Med Ctr, Inst Metab Dis, Dallas, TX USA Baylor Univ Dallas TX USA Univ, Med Ctr, Inst Metab Dis, Dallas, TX USA
Titolo Testata:
NATURE GENETICS
fascicolo: 2, volume: 29, anno: 2001,
pagine: 212 - 216
SICI:
1061-4036(200110)29:2<212:PROLSI>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-HYDROXYBUTYRIC ACID; GABA(B) RECEPTORS; RAT HIPPOCAMPUS; TAURINE RELEASE; BINDING-SITES; FIRING RATE; BRAIN; ACTIVATION; CELLS; NEURONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Gibson, KM Oregon Hlth Sci Univ, Dept Mol & Med Genet, 2525 SW 3rd Ave, Portland, OR 97201 USA Oregon Hlth Sci Univ 2525 SW 3rd Ave Portland OR USA 97201 USA
Citazione:
B.M. Hogema et al., "Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase", NAT GENET, 29(2), 2001, pp. 212-216

Abstract

Succinate semialdehyde dehydrogenase (ALDH5A1, encoding SSADH deficiency is a defect of 4-aminobutyric acid (GABA) degradation that manifests in humans as 4-hydroxybutyric (gamma-hydroxybutyric, GHB) aciduria. It is characterized by a non-specific neurological disorder including psychomotor retardation, language delay, seizures, hypotonia and ataxia. The current therapy, vigabatrin (VGB), is not uniformly successful(1). Here we report the development of Aldh5a1-deficient mice. At postnatal day 16-22 Aldh5a1(-/-) mice display ataxia and develop generalized seizures leading to rapid death. We observed increased amounts of GHB and total GABA in urine, brain and liver homogenates and detected significant gliosis in the hippocampus of Aldh5a1(-/-) mice. We found therapeutic intervention with phenobarbital or pherytoinineffective, whereas intervention with vigabatrin or the GABA(B) receptor antagonist CGP 35348 (ref. 2) prevented tonic-clonic convulsions and significantly enhanced survival of the mutant mice. Because neurologic deterioration coincided with weaning, we hypothesized the presence of a protective compound in breast milk. Indeed, treatment of mutant mice with the amino acidtaurine rescued Aldh5a1(-/-) mice. These findings provide insight into pathomechanisms and may have therapeutic relevance for the human SSADH deficiency disease and GHB overdose and toxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 16:59:09