Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperSynaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal
Highlights
▶We show progressive synaptic plasticity deficits in a mouse model of Rett syndrome. ▶Plasticity deficits track the onset and progression of Rett-like signs. ▶Synaptic plasticity deficits are consistent with a saturation or ceiling effect. ▶Short-term plasticity deficit is partially reversed by the memantine.
Section snippets
Mecp2-stop mice
Heterozygous female Mecp2-stop mice (Mecp2stop/+ genotype) in which one endogenous Mecp2 allele is silenced by a targeted STOP cassette (Guy et al., 2007) were obtained from the laboratory of Prof. Adrian Bird (University of Edinburgh, Edinburgh, UK). A local colony was established by breeding heterozygous Mecp2stop/+ females with wild-type males. All mice used in experiments were hemizygous Mecp2stop/y males and wild-type male littermates resulting from a breeding scheme involving at least six
Robust silencing of MeCP2 expression in the Mecp2-stop mouse model
Western blot analysis confirmed the absence of detectable MeCP2 in the brains of the hemizygous Mecp2stop/y mice (Fig. 1A) used in this study. This conclusion was supported by the absence of detectable MeCP2 within the hippocampal formation of these mice by immunohistochemistry (Fig. 1B). In contrast, in wild-type mice strong MeCP2 signal was detected from a similar amount of protein in the Western analysis and strong expression was apparent in the majority of cell nuclei in the hippocampal
Discussion
The current study demonstrates robust evidence for deficits in both short- and long-term forms of hippocampal synaptic plasticity in the brain of hemizygous mice in which Mecp2 expression has been prevented by targeted STOP cassette. These findings are in agreement with reports of deficits in previous studies conducted on Mecp2-null mice (Asaka et al., 2006) and in mice expressing a truncated form of MeCP2 (Moretti et al., 2006). An important observation is that hippocampal LTP is not impaired
Acknowledgments
We are grateful to the MRC (award G0800401) and Rett Syndrome Association Scotland (RSA-S) for support. SMW is funded by a studentship from the Taiwan government. We thank Imre Vida for comments on the manuscript.
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