Researchers at Oregon Health & Science University have discovered that a molecule¹ critical to the development and plasticity（可塑性） of nerve cells - brain-derived neurotrophic factor (BDNF) - is severely² lacking in brainstem neurons in mutations leading to Rett syndrome⁴, a neurological developmental disorder⁵. The finding has implications for the treatment of neurological disorders⁶, including Rett syndrome that affects one in 10,000 baby girls. The new discovery is published online in Neuroscience 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 miserably⁷ at making BDNF. When normal neurons are faced with a respiratory（呼吸的） 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 gene⁸ mutation³. 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 previously⁹ published data that show BDNF is involved in normal maturation of neuronal pathways controlling cardiorespiratory（心和肺的） function, could play a significant role in the development of a treatment for Rett syndrome," said Agnieszka Balkowiec, M.D., Ph.D., principal investigator¹⁰ and associate professor of integrative biosciences in the OHSU School of Dentistry; and adjunct assistant professor of physiology¹¹ 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 doctorate¹² 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 Dimes¹³; and International Rett Syndrome Foundation.