Open AccessD-cycloserine improves synaptic transmission in an animal mode of Rett syndrome
Author(s) -
Elisa S. Na,
Héctor De Jesús-Cortés,
Arlene Martínez-Rivera,
Zeeba D. Kabir,
Jieqi Wang,
Vijayashree Ramesh,
Yasemin Onder,
Anjali M. Rajadhyaksha,
Lisa M. Monteggia,
Andrew A. Pieper
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0183026
Subject(s) - rett syndrome , mecp2 , neuroscience , long term potentiation , neurotransmission , hippocampus , neurodevelopmental disorder , hippocampal formation , medicine , psychology , biology , autism , psychiatry , phenotype , genetics , receptor , gene
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 Mecp2 tm1 . 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 Mecp2 tm1 . 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.