Abstract
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) antagonists 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 106-119 |
| Number of pages | 14 |
| Journal | Brain Research |
| Volume | 1380 |
| DOIs | |
| State | Published - Mar 22 2011 |
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Keywords
- Fragile X syndrome
- Lithium
- Long-term depression
- LY341495
- Metabotropic glutamate receptor
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment. / Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Paul; Kollaros, Maria; Gertner, Michael J.; Woo, Newton H.; Tranfaglia, Michael R.; Bear, Mark F.; Zukin, R. Suzanne; McDonald, Thomas V.; Jongens, Thomas A.; McBride, Sean M J.
In: Brain Research, Vol. 1380, 22.03.2011, p. 106-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment
AU - Choi, Catherine H.
AU - Schoenfeld, Brian P.
AU - Bell, Aaron J.
AU - Hinchey, Paul
AU - Kollaros, Maria
AU - Gertner, Michael J.
AU - Woo, Newton H.
AU - Tranfaglia, Michael R.
AU - Bear, Mark F.
AU - Zukin, R. Suzanne
AU - McDonald, Thomas V.
AU - Jongens, Thomas A.
AU - McBride, Sean M J
PY - 2011/3/22
Y1 - 2011/3/22
N2 - 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) antagonists 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.
AB - 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) antagonists 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.
KW - Fragile X syndrome
KW - Lithium
KW - Long-term depression
KW - LY341495
KW - Metabotropic glutamate receptor
UR - http://www.scopus.com/inward/record.url?scp=79952315521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952315521&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2010.11.032
DO - 10.1016/j.brainres.2010.11.032
M3 - Article
C2 - 21078304
AN - SCOPUS:79952315521
VL - 1380
SP - 106
EP - 119
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -