Document Detail


Traumatic Brain Injury Increased IGF-1B mRNA and Altered IGF1 Exon 5 and Promoter Region Epigenetic Characteristics in the Rat Pup Hippocampus.
MedLine Citation:
PMID:  22413999     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Traumatic brain injury (TBI) is a major cause of acquired cognitive disability in childhood. Such disability may be blunted by enhancing the brain's endogenous neuroprotective response. An important endogenous neuroprotective response is the insulin-like growth factor 1(IGF-1) mRNA variant, IGF-1B. IGF-1B mRNA, characterized by exon 5 inclusion, encodes the IGF-1 and the Eb peptides. IGF-1A mRNA excludes exon 5 and encodes the IGF-1 and Ea peptides. A region in the human IGF-1B homologue acts as an exon splicing enhancer (ESE) to increase IGF-1B mRNA. It is not known if TBI is associated with increased brain IGF-1B mRNA. Epigenetic modifications may underlie altered gene expression in the brain after TBI. We hypothesized that TBI would increase hippocampal IGF-1B mRNA in 17 day old rats, associated with DNA methylation and/or histone modifications at the promoter site 1 (P1) or exon 5/ESE region. Hippocampi from rat pups after controlled cortical impact (CCI) were used to measure IGF-1B mRNA, DNA methylation and histone modifications at the P1, P2 and exon5/ESE regions. In CCI hippocampi, IGF1B mRNA peaked at post injury day (PID) 2 (1700± 320% SHAM) but normalized by PID14. IGF-1A peaked at PID3 (280± 52% SHAM) and remained elevated at PID14. Increased IGF-1B mRNA was associated with increased methylation at P1, increased histone modifications associated with gene activation at P2 and exon5/ESE, together with differential methylation in the exon 5/ESE regions. We report for the first time that hippocampal IGF-1BmRNA increased after developmental TBI. We speculate that epigenetic modifications at the P2 and exon 5/ESE regions are important in the regulation of IGF-1B mRNA expression. The exon 5/ESE region may be a target for future therapies to target IGF-1B transcription after TBI.
Authors:
Michelle Elena Schober; Xingrao Ke; Bohan Xing; Benjamin P Block; Daniela Requena; Robert McKnight; Robert Henry Lane
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-13
Journal Detail:
Title:  Journal of neurotrauma     Volume:  -     ISSN:  1557-9042     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Utah, Pediatric Critical Care, 3046 Lehua Lane, salt lake city, Utah, United States, 84117, 801 450 8895, 801 5857395; michelle.schober@hsc.utah.edu.
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