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Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2007 Oct 03; Vol. 27 (40), pp. 10685-94. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Actins metabolism
Analysis of Variance
Animals
Cofilin 1 metabolism
Dendritic Spines drug effects
Dendritic Spines metabolism
Disease Models, Animal
Electric Stimulation methods
Excitatory Postsynaptic Potentials genetics
Fragile X Mental Retardation Protein genetics
Fragile X Syndrome drug therapy
Fragile X Syndrome genetics
Gene Expression Regulation drug effects
Hippocampus pathology
In Vitro Techniques
Long-Term Potentiation physiology
Long-Term Potentiation radiation effects
Mice
Mice, Knockout
Neurons pathology
Neurons radiation effects
Patch-Clamp Techniques
Receptors, N-Methyl-D-Aspartate physiology
Brain-Derived Neurotrophic Factor pharmacology
Excitatory Postsynaptic Potentials drug effects
Fragile X Syndrome pathology
Long-Term Potentiation drug effects
Neurons drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 27
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 17913902
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.2624-07.2007