Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome

F Fernandez, W Morishita, E Zuniga, J Nguyen… - Nature …, 2007 - nature.com
F Fernandez, W Morishita, E Zuniga, J Nguyen, M Blank, RC Malenka, CC Garner
Nature neuroscience, 2007nature.com
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 …
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.
nature.com