D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome

Elisa S Na; Hector de Jesus-Cortes; Arlene Martinez-Rivera; Zeeba D Kabir; Jieqi Wang; Vijayashree Ramesh; Yasemin Onder; Anjali M Rajadhyaksha; Lisa M Monteggia; Andrew A Pieper

doi:10.1371/journal.pone.0183026

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D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome

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D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome

Elisa S Na, Hector de Jesus-Cortes, Arlene Martinez-Rivera, Zeeba D Kabir, Jieqi Wang, Vijayashree Ramesh, Yasemin Onder, Anjali M Rajadhyaksha, Lisa M Monteggia and Andrew A Pieper

PloS one, Vol.12(8), p.e0183026

08/16/2017

DOI: 10.1371/journal.pone.0183026

PMCID: PMC5559075

PMID: 28813484

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Abstract

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.

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Title: Subtitle: D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome
Creators: Elisa S Na - Texas Woman's University
Hector de Jesus-Cortes
Arlene Martinez-Rivera - Cornell University
Zeeba D Kabir - Cornell University
Jieqi Wang - University of Iowa
Vijayashree Ramesh - The University of Texas Southwestern Medical Center
Yasemin Onder - The University of Texas Southwestern Medical Center
Anjali M Rajadhyaksha - Cornell University
Lisa M Monteggia - The University of Texas Southwestern Medical Center
Andrew A Pieper - University of Iowa
Resource Type: Journal article
Publication Details: PloS one, Vol.12(8), p.e0183026
DOI: 10.1371/journal.pone.0183026
PMID: 28813484
PMCID: PMC5559075
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: PUBLIC LIBRARY SCIENCE
Number of pages: 16
Grant note: Rett Syndrome Research Trust Weill Cornell Autism Research Program MH081060 / NIMH The Hartwell Foundation
Language: English
Date published: 08/16/2017
Academic Unit: Psychiatry
Record Identifier: 9984230422902771

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