D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome
| Autor: | Arlene Martinez-Rivera, Andrew A. Pieper, Héctor De Jesús-Cortés, Jieqi Wang, Lisa M. Monteggia, Anjali M. Rajadhyaksha, Elisa S. Na, Yasemin Onder, Vijayashree Ramesh, Zeeba D. Kabir |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonology Physiology Apnea lcsh:Medicine Hippocampus Striatum Hippocampal formation Mice 0302 clinical medicine Medicine and Health Sciences Medicine Enzyme-Linked Immunoassays lcsh:Science Mammals Multidisciplinary Respiration Brain Long-term potentiation Animal Models Experimental Organism Systems Breathing Vertebrates Anatomy Gait Analysis Brainstem Research Article congenital hereditary and neonatal diseases and abnormalities Neural facilitation Rett syndrome Mouse Models Neurotransmission Research and Analysis Methods Rodents MECP2 03 medical and health sciences Model Organisms Animals Immunoassays business.industry Biological Locomotion lcsh:R Organisms Biology and Life Sciences medicine.disease Neostriatum 030104 developmental biology nervous system Amniotes Immunologic Techniques lcsh:Q business Physiological Processes Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 8, p e0183026 (2017) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|