期刊
BRAIN RESEARCH
卷 1380, 期 -, 页码 106-119出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2010.11.032
关键词
Fragile X syndrome; Long-term depression; Lithium; Metabotropic glutamate receptor; LY341495
资金
- FRAXA Research Foundation
- National Fragile X Foundation
- Autism Speaks
- Albert Einstein College of Medicine
- NIH-NINDS
- NIGMS
Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonism or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome. (C) 2010 Elsevier B.V. All rights reserved.
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