Potential Therapeutic Target In Down Syndrome

Down syndrome is the most common form of human mental retardation and is caused by the triplication of chromosome 21. Individuals with Down syndrome often have deficits in their memory for facts and events, called declarative memory. The Down syndrome model mouse, which has an extra copy of a segment of chromosome 16 - homologous to human chromosome 21 - shows some of the features of the human disorder, including deficits in declarative memory. The mutant mice also demonstrate excessive inhibition - mediated by the neurotransmitter GABA - in their brains.

Craig Garner and colleagues report that subtly reducing inhibitory function in these mice can rescue their cognitive deficits. The authors treated Down syndrome mice for two weeks with one of two drugs that inhibit the GABA receptor. Both drugs improved their performance in two declarative memory tasks. Moreover, this improvement lasted for up to two months after the drug treatment was stopped. The authors also found a normalization of long-term potentiation, which is the ability of synapses to undergo long-lasting changes in synaptic strength, considered a correlate of learning and memory. Although these findings need to be validated by clinical studies, they suggest that GABA might represent a potential therapeutic target to improve cognitive impairments in Down syndrome.

Author contact:

Craig Garner (Stanford University, Palo Alto, CA, USA)
E-mail: cgarner@stanford.edu

Abstract available online.

(C) Nature Neuroscience press release.

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