Journal Article

DZNE-2020-05503

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

Colas, D. (Corresponding author) ; Chuluun, B. (Corresponding author) ; Garner, C. C. (Corresponding author)DZNE* ; Heller, H. C. (Corresponding author)

2017
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.nlm.2017.02.006

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.

Keyword(s): Animals (MeSH) ; Cognition: drug effects (MeSH) ; Disease Models, Animal (MeSH) ; Down Syndrome: drug therapy (MeSH) ; Down Syndrome: genetics (MeSH) ; Flumazenil: pharmacology (MeSH) ; Flumazenil: therapeutic use (MeSH) ; GABA Modulators: pharmacology (MeSH) ; GABA Modulators: therapeutic use (MeSH) ; Male (MeSH) ; Memory Disorders: drug therapy (MeSH) ; Memory, Long-Term: drug effects (MeSH) ; Mice (MeSH) ; GABA Modulators ; Flumazenil

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Contributing Institute(s):

1. Synaptopathy (AG Garner)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Social Sciences Citation Index ; Web of Science Core Collection

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