PMID- 26592967 OWN - NLM STAT- MEDLINE DCOM- 20161018 LR - 20200106 IS - 1873-474X (Electronic) IS - 0736-5748 (Linking) VI - 48 DP - 2016 Feb TI - Neonatal hyperoxia induces alterations in neurotrophin gene expression. PG - 31-7 LID - S0736-5748(15)30104-0 [pii] LID - 10.1016/j.ijdevneu.2015.11.003 [doi] AB - Each year in the United States, nearly 500,000 infants a year are born prematurely. Babies born before 35 weeks gestation are often placed on ventilators and/or given supplemental oxygen. This increase in oxygen, while critical for survival, can cause long-term damage to lungs, retinas and brains. In particular, hyperoxia causes apoptosis in neurons and alters glial activity. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are members of the neurotrophin family of proteins that function to promote the growth, differentiation and development of the nervous system. We hypothesized that hyperoxia can alter the regulation of these genes and by doing so adversely affect the development of the brain. We predicted that mice exposed to hyperoxic conditions would have differences in BDNF and GDNF mRNA expression and relative level of methylated promoter regions coinciding with differences in the relative levels of DNMT1 and DNMT3a mRNA expression. To test this hypothesis, newborn C57Bl/6 mice and their littermates were placed in hyperoxic or normoxic conditions from postnatal day 7 to 12. There were significant decreases in BDNF mRNA expression in the prefrontal cortex following hyperoxia, but a significant increase in the isocortex. GDNF mRNA expression was significantly increased in both the isocortex and prefrontal cortex following hyperoxia. DNMT1 mRNA expression was significantly decreased in the isocortex but significantly increased in the prefrontal following hyperoxia. Together these data suggest that short-term exposure to hyperoxic conditions can affect the regulation and expression of BDNF and GDNF potentially leading to alterations in neural development. CI - Published by Elsevier Ltd. FAU - Sengoku, T AU - Sengoku T AD - University of Kentucky, Department of Physiology, 800 Rose Street, MS 508, Lexington, KY 40536, USA. FAU - Murray, K M AU - Murray KM AD - University of Kentucky, Department of Physiology, 800 Rose Street, MS 508, Lexington, KY 40536, USA. FAU - Wilson, M E AU - Wilson ME AD - University of Kentucky, Department of Physiology, 800 Rose Street, MS 508, Lexington, KY 40536, USA. Electronic address: melinda.wilson@uky.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20151122 PL - United States TA - Int J Dev Neurosci JT - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience JID - 8401784 RN - 0 (Aif1 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium-Binding Proteins) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Microfilament Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Olig2 protein, mouse) RN - 0 (Oligodendrocyte Transcription Factor 2) RN - 0 (RNA, Messenger) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNMT1 protein, human) RN - EC 2.1.1.37 (Dnmt1 protein, mouse) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) SB - IM MH - Analysis of Variance MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium-Binding Proteins/metabolism MH - Cerebral Cortex/*growth & development/*metabolism MH - DNA (Cytosine-5-)-Methyltransferase 1 MH - DNA (Cytosine-5-)-Methyltransferases/genetics/metabolism MH - Female MH - Gene Expression Regulation, Developmental/*physiology MH - Glial Cell Line-Derived Neurotrophic Factor/genetics/*metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Humans MH - Hyperoxia/metabolism/*pathology MH - Infant, Newborn MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microfilament Proteins/metabolism MH - Nerve Tissue Proteins/metabolism MH - Oligodendrocyte Transcription Factor 2 MH - Phosphopyruvate Hydratase/metabolism MH - Pregnancy MH - RNA, Messenger/metabolism OTO - NOTNLM OT - BDNF OT - DNA methylation OT - DNMT1 OT - DNMT3a OT - GDNF OT - Hyperoxia EDAT- 2015/11/26 06:00 MHDA- 2016/10/19 06:00 CRDT- 2015/11/24 06:00 PHST- 2015/09/03 00:00 [received] PHST- 2015/11/13 00:00 [revised] PHST- 2015/11/14 00:00 [accepted] PHST- 2015/11/24 06:00 [entrez] PHST- 2015/11/26 06:00 [pubmed] PHST- 2016/10/19 06:00 [medline] AID - S0736-5748(15)30104-0 [pii] AID - 10.1016/j.ijdevneu.2015.11.003 [doi] PST - ppublish SO - Int J Dev Neurosci. 2016 Feb;48:31-7. doi: 10.1016/j.ijdevneu.2015.11.003. Epub 2015 Nov 22.