Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down's syndrome

Abstract

Down's syndrome (DS) is the most prevalent genetic intellectual disability. Memory deficits significantly contribute to the cognitive dysfunction in DS. Previously, we discovered that mTOR-dependent local translation, a pivotal process for some forms of synaptic plasticity, is deregulated in a DS mouse model. Here, we report that these mice exhibit deficits in both synaptic plasticity (i.e., BDNF-long term potentiation) and the persistence of spatial long-term memory. Interestingly, these deficits were fully reversible using rapamycin, a Food and Drug Administration-approved specific mTOR inhibitor; therefore, rapamycin may be a novel pharmacotherapy to improve cognition in DS.

Keywords: BDNF-LTP; Barnes maze; ERK; MTOR; Pharmacotherapy; Rapamycin; Synaptic plasticity; Trisomy 21; Ts1Cje.