PMID- 17913902
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 40
DP  - 2007 Oct 3
TI  - Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of 
      fragile X syndrome.
PG  - 10685-94
AB  - Mice lacking expression of the fragile X mental retardation 1 (Fmr1) gene have 
      deficits in types of learning that are dependent on the hippocampus. Here, we 
      report that long-term potentiation (LTP) elicited by threshold levels of theta 
      burst afferent stimulation (TBS) is severely impaired in hippocampal field CA1 of 
      young adult Fmr1 knock-out mice. The deficit was not associated with changes in 
      postsynaptic responses to TBS, NMDA receptor activation, or levels of punctate 
      glutamic acid decarboxylase-65/67 immunoreactivity. TBS-induced actin 
      polymerization within dendritic spines was also normal. The LTP impairment was 
      evident within 5 min of induction and, thus, may not be secondary to defects in 
      activity-initiated protein synthesis. Protein levels for both brain-derived 
      neurotrophic factor (BDNF), a neurotrophin that activates pathways involved in 
      spine cytoskeletal reorganization, and its TrkB receptor were comparable between 
      genotypes. BDNF infusion had no effect on baseline transmission or on 
      postsynaptic responses to theta burst stimulation, but nonetheless fully restored 
      LTP in slices from fragile X mice. These results indicate that the fragile X 
      mutation produces a highly selective impairment to LTP, possibly at a step 
      downstream of actin filament assembly, and suggest a means for overcoming this 
      deficit. The possibility of a pharmacological therapy based on these results is 
      discussed.
FAU - Lauterborn, Julie C
AU  - Lauterborn JC
AD  - Department of Anatomy and Neurobiology, University of California, Irvine, 
      California 92697-4292, USA. jclauter@uci.edu
FAU - Rex, Christopher S
AU  - Rex CS
FAU - Kramar, Eniko
AU  - Kramar E
FAU - Chen, Lulu Y
AU  - Chen LY
FAU - Pandyarajan, Vijay
AU  - Pandyarajan V
FAU - Lynch, Gary
AU  - Lynch G
FAU - Gall, Christine M
AU  - Gall CM
LA  - eng
GR  - R03 HD051829/HD/NICHD NIH HHS/United States
GR  - R01 NS051823/NS/NINDS NIH HHS/United States
GR  - AG00358/AG/NIA NIH HHS/United States
GR  - R01 NS037799/NS/NINDS NIH HHS/United States
GR  - NS051823/NS/NINDS NIH HHS/United States
GR  - NS37799/NS/NINDS NIH HHS/United States
GR  - HD51829/HD/NICHD NIH HHS/United States
GR  - NS045260/NS/NINDS NIH HHS/United States
GR  - P01 NS045260/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cofilin 1)
RN  - 0 (Fmr1 protein, mouse)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Actins/metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cofilin 1/metabolism
MH  - Dendritic Spines/drug effects/metabolism
MH  - Disease Models, Animal
MH  - Electric Stimulation/methods
MH  - Excitatory Postsynaptic Potentials/*drug effects/genetics
MH  - Fragile X Mental Retardation Protein/genetics
MH  - Fragile X Syndrome/drug therapy/genetics/*pathology
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/pathology
MH  - In Vitro Techniques
MH  - Long-Term Potentiation/*drug effects/physiology/radiation effects
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*drug effects/pathology/radiation effects
MH  - Patch-Clamp Techniques
MH  - Receptors, N-Methyl-D-Aspartate/physiology
PMC - PMC6672822
EDAT- 2007/10/05 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/04/03
CRDT- 2007/10/05 09:00
PHST- 2007/10/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/10/05 09:00 [entrez]
PHST- 2008/04/03 00:00 [pmc-release]
AID - 27/40/10685 [pii]
AID - 3270623 [pii]
AID - 10.1523/JNEUROSCI.2624-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Oct 3;27(40):10685-94. doi: 10.1523/JNEUROSCI.2624-07.2007.