OHSU discovery may lead to new treatment for Rett Syndrome

The research, published in Neuroscience, sheds light on what determines availability of the molecules involved in cardiorespiratory control

2012-01-30

(Press-News.org) Researchers at Oregon Health & Science University (http://www.ohsu.edu) have discovered that a molecule critical to the development and plasticity of nerve cells – brain-derived neurotrophic factor (BDNF) -- is severely lacking in brainstem neurons in mutations leading to Rett syndrome, a neurological developmental disorder. The finding has implications for the treatment of neurological disorders, including Rett syndrome that affects one in 10,000 baby girls.

The new discovery is published online in Neuroscience (http://www.sciencedirect.com/science/article/pii/S0306452212000395?v=s5) and is expected in the print issue of Neuroscience in March.

Using a mouse model of Rett syndrome, the OHSU team found that mutant neurons in the brainstem fail miserably at making BDNF. When normal neurons are faced with a respiratory challenge, such as low oxygen, they dramatically increase the production of BDNF, whereas mutant neurons do not.

According to the National Institutes of Health, Rett syndrome is estimated to affect one in every 10,000 to 15,000 live births and almost exclusively girls because it is caused by an X-linked gene mutation. In addition to severe problems with motor function, other symptoms of Rett syndrome may include breathing difficulties while awake.

"The new finding, coupled with our previously published data that show BDNF is involved in normal maturation of neuronal pathways controlling cardiorespiratory function, could play a significant role in the development of a treatment for Rett syndrome," said Agnieszka Balkowiec, M.D., Ph.D., principal investigator and associate professor of integrative biosciences in the OHSU School of Dentistry; and adjunct assistant professor of physiology and pharmacology in the OHSU School of Medicine. To conduct this research, Balkowiec partnered with John M. Bissonnette, M.D., professor of obstetrics and gynecology, and cell and developmental biology in the OHSU School of Medicine.

### Additional study authors include: Anke Vermehren-Schmaedick, Ph.D., OHSU Department of Biomedical Engineering; Victoria K. Jenkins, B.A., who is currently pursuing her doctorate at Boston University; and Sharon J. Knopp, a research assistant in Bissonnette's lab.

The study was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health; March of Dimes; and International Rett Syndrome Foundation.

ABOUT OHSU Oregon Health & Science University is the state's only health and research university. As Portland's largest employer, OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. OHSU serves patients from every corner of the state and is a conduit for learning for more than 4,300 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to each county in the state.

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