Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment

被引：79

作者：

Choi, Catherine H. ^{[1
,2
,3
,4
]}

Schoenfeld, Brian P. ^{[1
,2
]}

Bell, Aaron J. ^{[1
,2
]}

Hinchey, Paul ^{[1
,2
]}

Kollaros, Maria ^{[1
,2
]}

Gertner, Michael J. ^{[5
]}

Woo, Newton H. ^{[6
]}

Tranfaglia, Michael R. ^{[7
]}

Bear, Mark F. ^{[8
,9
]}

Zukin, R. Suzanne ^{[5
]}

McDonald, Thomas V. ^{[1
,2
]}

Jongens, Thomas A. ^{[10
]}

McBride, Sean M. J. ^{[1
,2
,11
]}

机构：

[1] Albert Einstein Coll Med, Sect Mol Cardiol, Dept Med, Bronx, NY 10461 USA

[2] Albert Einstein Coll Med, Sect Mol Cardiol, Dept Mol Pharmacol, Bronx, NY 10461 USA

[3] Lehigh Valley Hosp, Lehigh Valley Hlth Syst, Dept Med, Allentown, PA 18103 USA

[4] Drexel Univ, Coll Med, Dept Dermatol, Philadelphia, PA 19102 USA

[5] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA

[6] OND CDER FDA, Div Anesthesia & Analgesia Prod, Off Drug Evaluat 2, Silver Spring, MD 20993 USA

[7] FRAXA Res Fdn, Newburyport, MA USA

[8] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA

[9] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

[10] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[11] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA

来源：

BRAIN RESEARCH | 2011年 / 1380卷

关键词：

Fragile X syndrome; Long-term depression; Lithium; Metabotropic glutamate receptor; LY341495; METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM DEPRESSION; MENTAL-RETARDATION PROTEIN; FREELY MOVING RATS; HIPPOCAMPAL CA1 REGION; IN-VIVO; DENTATE GYRUS; COGNITIVE IMPAIRMENT; SELECTIVE ANTAGONIST; SPATIAL MEMORY;

D O I：

10.1016/j.brainres.2010.11.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：106 / 119

页数：14

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