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

Elisa S. Na, Héctor De Jesús-Cortés, Arlene Martinez-Rivera, Zeeba D. Kabir, Jieqi Wang, Vijayashree Ramesh, Yasemin Onder, Anjali M. Rajadhyaksha, Lisa M Monteggia, Andrew A. Pieper

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 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.

Original languageEnglish (US)
Article numbere0183026
JournalPLoS One
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

cycloserine
Cycloserine
Rett Syndrome
synaptic transmission
Synaptic Transmission
Animals
Brain-Derived Neurotrophic Factor
signs and symptoms (animals and humans)
Brain
mice
Long-Term Potentiation
amino acid derivatives
animals
brain stem
synapse
Alanine
alanine
Genes
X-Linked Genes
antibiotics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Na, E. S., De Jesús-Cortés, H., Martinez-Rivera, A., Kabir, Z. D., Wang, J., Ramesh, V., ... Pieper, A. A. (2017). D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome. PLoS One, 12(8), [e0183026]. https://doi.org/10.1371/journal.pone.0183026

D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome. / Na, Elisa S.; De Jesús-Cortés, Héctor; Martinez-Rivera, Arlene; Kabir, Zeeba D.; Wang, Jieqi; Ramesh, Vijayashree; Onder, Yasemin; Rajadhyaksha, Anjali M.; Monteggia, Lisa M; Pieper, Andrew A.

In: PLoS One, Vol. 12, No. 8, e0183026, 01.08.2017.

Research output: Contribution to journalArticle

Na, ES, De Jesús-Cortés, H, Martinez-Rivera, A, Kabir, ZD, Wang, J, Ramesh, V, Onder, Y, Rajadhyaksha, AM, Monteggia, LM & Pieper, AA 2017, 'D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome', PLoS One, vol. 12, no. 8, e0183026. https://doi.org/10.1371/journal.pone.0183026
Na ES, De Jesús-Cortés H, Martinez-Rivera A, Kabir ZD, Wang J, Ramesh V et al. D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome. PLoS One. 2017 Aug 1;12(8). e0183026. https://doi.org/10.1371/journal.pone.0183026
Na, Elisa S. ; De Jesús-Cortés, Héctor ; Martinez-Rivera, Arlene ; Kabir, Zeeba D. ; Wang, Jieqi ; Ramesh, Vijayashree ; Onder, Yasemin ; Rajadhyaksha, Anjali M. ; Monteggia, Lisa M ; Pieper, Andrew A. / D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome. In: PLoS One. 2017 ; Vol. 12, No. 8.
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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 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.",
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