Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome
| Autor: | James H. Eubanks, Reiko Maki Fitzsimonds, Yukiko Asaka, Denis G.M. Jugloff, Liang Zhang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Methyl-CpG-Binding Protein 2
Long-Term Potentiation Rett syndrome Neurotransmission Hippocampal formation Biology Hippocampus Receptors N-Methyl-D-Aspartate Synaptic Transmission lcsh:RC321-571 MECP2 Mice Neurodevelopmental disorder mental disorders Rett Syndrome medicine Animals Theta Rhythm lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Neuronal Plasticity Glutamate receptor Excitatory Postsynaptic Potentials Mental retardation Long-term potentiation medicine.disease Mice Mutant Strains Mice Inbred C57BL Cytoskeletal Proteins Disease Models Animal nervous system Neurology Synaptic plasticity LTD LTP Neuroscience |
| Zdroj: | Neurobiology of Disease, Vol 21, Iss 1, Pp 217-227 (2006) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2005.07.005 |
| Popis: | Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in the gene encoding the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Here we demonstrate that the Mecp2-null mouse model of Rett syndrome shows an age-dependent impairment in hippocampal CA1 long-term potentiation induced by tetanic or theta-burst stimulation. Long-term depression induced by repetitive low-frequency stimulation is also absent in behaviorally symptomatic Mecp2-null mice. Immunoblot analyses from behaviorally symptomatic Mecp2-null mice reveal altered expression of N-methyl-d-aspartate receptor subunits NR2A and NR2B. Presynaptic function is also affected, as demonstrated by a significant reduction in paired-pulse facilitation. Interestingly, the properties of basal neurotransmission are normal in the Mecp2-null mice, consistent with our observations that the levels of expression of synaptic and cytoskeletal proteins, including glutamate receptor subunits GluR1 and GluR2, PSD95, synaptophysin-1, synaptobrevin-2, synaptotagmin-1, MAP2, betaIII-tubulin and NF200, are not significantly altered. Together, these data provide the first evidence that the loss of Mecp2 expression is accompanied by age-dependent alterations in excitatory synaptic plasticity that are likely to contribute to the cognitive and functional deficits underlying Rett syndrome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect