Rett syndrome is a neurodevelopmental disorder caused by loss-of-function 
mutations in the gene encoding the transcription factor methyl-CpG-binding 
protein 2 (MeCP2). One of its targets is the gene encoding brain-derived 
neurotrophic factor (bdnf). In vitro studies using cultured neurons have 
produced conflicting results with respect to the role of MeCP2 in BDNF 
expression. Acute intermittent hypoxia (AIH) induces plasticity in the 
respiratory system characterized by long-term facilitation of phrenic nerve 
amplitude. This paradigm induces an increase in BDNF protein. We hypothesized 
that AIH leads to augmentation of BDNF transcription in respiratory-related 
areas of the brainstem and that MeCP2 is necessary for this process. Wild-type 
and mecp2 null (mecp2(-/y)) mice were subjected to three 5-min episodes of 
exposure to 8% O(2)/4% CO(2)/88% N(2), delivered at 5-min intervals. Normoxia 
control wild-type and mecp2 null mice were exposed to room air for the total 
length of time, that is, 30 min. Following a recovery in room air, the pons and 
medulla were rapidly removed. Expression of BDNF protein and transcripts were 
determined by ELISA and quantitative PCR, respectively. AIH induced a 
significant increase in BDNF protein in the pons and medulla, and in mRNA 
transcript levels in the pons of wild-type animals. In contrast, there were no 
significant changes in either BDNF protein or transcripts in the pons or medulla 
of mice lacking MeCP2. The results indicate that MeCP2 is required for 
regulation of BDNF expression by acute intermittent hypoxia in vivo.