Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.
Neurobiol Learn Mem
; 140: 11-16, 2017 Apr.
Article
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| MEDLINE
| ID: mdl-28215510
ABSTRACT
Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABAA receptor (GABAAR) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABAAR antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Flumazenil
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Síndrome de Down
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Moduladores del GABA
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Memoria a Largo Plazo
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Trastornos de la Memoria
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article