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Brain derived neurotrophic factor alleviates disease symptoms in a mouse model of Rett Syndrome

Scientists from the Whitehead Institute for Biomedical Research, Brandeis University and Massachusetts Institute of Technology report in the February 2 issue of the journal Neuron that increasing levels of brain derived neurotrophic factor (BDNF) alleviates symptoms in a mouse model of the childhood disorder Rett Syndrome.

Rett Syndrome (RTT) is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

In late 2003 Rudolf Jaenisch of the Whitehead Institute and Michael Greenberg of Children's Hospital Boston announced that the "Rett Syndrome gene", Mecp2, interacts with bdnf. Interestingly, BDNF is highly active in infants aged 6 to 18 months, the same age that RTT symptoms first appear. BDNF is essential for neural plasticity (ability of neural circuits to undergo changes in function or organization due to previous activity), learning and memory. BDNF is also implicated in other neurological disorders including Huntington's Disease, schizophrenia and depression.

The bdnf/Mecp2 discovery, which was done in vitro (petri dishes and not live animals), raised the question of whether BDNF levels contribute to the devastating symptoms seen in RTT. To investigate the in vivo role (in a living organism) of BDNF in RTT Qiang Chang, a post-doctoral fellow in the Jaenisch lab, manipulated BDNF levels in the brains of genetically engineered "Rett mice". He discovered that deleting bdnf from the Mecp2 mutant mice resulted in an earlier onset and accelerated disease progression while increasing levels of BDNF led to a later onset and slower disease progression.
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Contact: Monica Coenraads
monica@rsrf.org
203-445-9233
Rett Syndrome Research Foundation
1-Feb-2006


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