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.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / metabolism*
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CA1 Region, Hippocampal / drug effects
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CA1 Region, Hippocampal / physiopathology
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Disease Models, Animal
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Down Syndrome / drug therapy*
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Down Syndrome / physiopathology
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Down Syndrome / psychology
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Long-Term Potentiation / drug effects*
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Long-Term Potentiation / physiology
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Male
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Maze Learning / drug effects
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Maze Learning / physiology
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Memory Disorders / drug therapy
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Memory, Long-Term / drug effects*
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Memory, Long-Term / physiology
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Nootropic Agents / pharmacology*
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Sirolimus / pharmacology*
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Spatial Memory / drug effects
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Spatial Memory / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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TOR Serine-Threonine Kinases / metabolism
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Tissue Culture Techniques
Substances
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Brain-Derived Neurotrophic Factor
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Nootropic Agents
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mTOR protein, mouse
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TOR Serine-Threonine Kinases
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Sirolimus