PMID- 22297041 OWN - NLM STAT- MEDLINE DCOM- 20120718 LR - 20211021 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 206 DP - 2012 Mar 29 TI - Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG-binding protein 2 null mice. PG - 1-6 LID - 10.1016/j.neuroscience.2012.01.017 [doi] AB - 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. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Vermehren-Schmaedick, A AU - Vermehren-Schmaedick A AD - Department of Integrative Biosciences, Oregon Health and Science University, Portland, OR 97239, USA. FAU - Jenkins, V K AU - Jenkins VK FAU - Knopp, S J AU - Knopp SJ FAU - Balkowiec, A AU - Balkowiec A FAU - Bissonnette, J M AU - Bissonnette JM LA - eng GR - HL076113/HL/NHLBI NIH HHS/United States GR - R01 HL076113-05/HL/NHLBI NIH HHS/United States GR - R01 HL076113-05S1/HL/NHLBI NIH HHS/United States GR - R01 HL076113/HL/NHLBI NIH HHS/United States GR - R01 HL076113-03/HL/NHLBI NIH HHS/United States GR - R01 HL076113-04/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120118 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Brain Stem/*metabolism MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Enzyme-Linked Immunosorbent Assay MH - Hypoxia/*metabolism MH - Methyl-CpG-Binding Protein 2/deficiency/*metabolism MH - Mice MH - Mice, Knockout MH - RNA, Messenger/analysis MH - Rett Syndrome/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC3293990 MID - NIHMS349463 EDAT- 2012/02/03 06:00 MHDA- 2012/07/19 06:00 PMCR- 2012/03/29 CRDT- 2012/02/03 06:00 PHST- 2011/09/30 00:00 [received] PHST- 2011/12/20 00:00 [revised] PHST- 2012/01/08 00:00 [accepted] PHST- 2012/02/03 06:00 [entrez] PHST- 2012/02/03 06:00 [pubmed] PHST- 2012/07/19 06:00 [medline] PHST- 2012/03/29 00:00 [pmc-release] AID - S0306-4522(12)00039-5 [pii] AID - 10.1016/j.neuroscience.2012.01.017 [doi] PST - ppublish SO - Neuroscience. 2012 Mar 29;206:1-6. doi: 10.1016/j.neuroscience.2012.01.017. Epub 2012 Jan 18.