Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome

Fabian Fernandez; Wade Morishita; Elizabeth Zuniga; James Nguyen; Martina Blank; Robert C. Malenka; Craig C. Garner

doi:10.1038/nn1860

Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome

Fabian Fernandez, Wade Morishita, Elizabeth Zuniga, James Nguyen, Martina Blank, Robert C. Malenka, Craig C. Garner

Research output: Contribution to journal › Article › peer-review

433 Scopus citations

Abstract

Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABA_A antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABA_A antagonists may be useful therapeutic agents for this disorder.

Original language	English (US)
Pages (from-to)	411-413
Number of pages	3
Journal	Nature neuroscience
Volume	10
Issue number	4
DOIs	https://doi.org/10.1038/nn1860
State	Published - Apr 2007
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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title = "Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome",

abstract = "Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABAA antagonists may be useful therapeutic agents for this disorder.",

author = "Fabian Fernandez and Wade Morishita and Elizabeth Zuniga and James Nguyen and Martina Blank and Malenka, {Robert C.} and Garner, {Craig C.}",

note = "Funding Information: We thank the Down Syndrome Research and Treatment Foundation (DSRTF), the Hillblom Foundation, the US National Science Foundation (NSF), the US National Institute of Health (NIH), Jax West Laboratories, the Stanford Down Syndrome Center and W.C. Mobley for their support.",

year = "2007",

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doi = "10.1038/nn1860",

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T1 - Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome

AU - Fernandez, Fabian

AU - Morishita, Wade

AU - Zuniga, Elizabeth

AU - Nguyen, James

AU - Blank, Martina

AU - Malenka, Robert C.

AU - Garner, Craig C.

N1 - Funding Information: We thank the Down Syndrome Research and Treatment Foundation (DSRTF), the Hillblom Foundation, the US National Science Foundation (NSF), the US National Institute of Health (NIH), Jax West Laboratories, the Stanford Down Syndrome Center and W.C. Mobley for their support.

PY - 2007/4

Y1 - 2007/4

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AB - Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABAA antagonists may be useful therapeutic agents for this disorder.

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Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome

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