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Titolo:
Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease
Autore:
Schmidt, N; Ferger, B;
Indirizzi:
Swiss Fed Inst Technol, Behav Neurobiol Lab, CH-8603 Schwerzenbach, Switzerland Swiss Fed Inst Technol Schwerzenbach Switzerland CH-8603 ch, Switzerland Univ Marburg, Fac Pharm, Inst Pharmacol, D-35032 Marburg, Germany Univ Marburg Marburg Germany D-35032 Pharmacol, D-35032 Marburg, Germany
Titolo Testata:
SYNAPSE
fascicolo: 1, volume: 40, anno: 2001,
pagine: 47 - 54
SICI:
0887-4476(200104)40:1<47:NEO(IT>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE ANTAGONISTS; IN-VIVO; MPP+ NEUROTOXICITY; GLUTAMATE-RELEASE; OXIDATIVE STRESS; SUBSTANTIA-NIGRA; BASAL GANGLIA; MICE; DOPAMINE; RATS;
Keywords:
dopamine; excitotoxicity; glutamate; neurodegeneration; substantia nigra;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Ferger, B Swiss Fed Inst Technol, Behav Neurobiol Lab, Schorenstr 16, CH-8603 Schwerzenbach, Switzerland Swiss Fed Inst Technol Schorenstr 16 Schwerzenbach Switzerland CH-8603
Citazione:
N. Schmidt e B. Ferger, "Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease", SYNAPSE, 40(1), 2001, pp. 47-54

Abstract

This is the first study to investigate the potential protective effects ofthe lipophilic kavapyrone (+/-)-kavain in the experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (+/-)-kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLCwith electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (+/-)-kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP+ (1-methyl-4-phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (+/-)-kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP-induced dopamine depletion, but a high dosage of(+/-)-kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP-induced decrease of TH-immunoreactivity as well as the loss of nigral neurons was completely prevented by (+/-)-kavain (200 mg/kg). Striatal MPP+ levels were not altered by (+/-)-kavain treatment. In conclusion, we found thatMPTP metabolism was not influenced by (+/-)-kavain and postulate the antiglutamatergic effects of (+/-)-kavain for its protective effects against MPTP toxicity. (+/-)-Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 10:32:07