|Title||D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Na ES, De Jesús-Cortés H, Martinez-Rivera A, Kabir ZD, Wang J, Ramesh V, Onder Y, Rajadhyaksha AM, Monteggia LM, Pieper AA|
|Keywords||Animals, Apnea, Brain Stem, Brain-Derived Neurotrophic Factor, Corpus Striatum, Cycloserine, Disease Models, Animal, Gait, Hippocampus, Locomotion, Male, Methyl-CpG-Binding Protein 2, Mice, Mice, Transgenic, Muscle Strength, Rett Syndrome, Synaptic Transmission, Tremor|
Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC5559075|