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Brain trauma induces X‐box protein 1 processing indicative of activation of the endoplasmic reticulum unfolded protein response
Author(s) -
Paschen Wulf,
Yatsiv Ido,
Shoham Shai,
Shohami Esther
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02218.x
Subject(s) - xbp1 , endoplasmic reticulum , striatum , hippocampus , unfolded protein response , messenger rna , endocrinology , medicine , cortex (anatomy) , hsp70 , biology , cerebral cortex , heat shock protein , microbiology and biotechnology , neuroscience , biochemistry , rna , gene , rna splicing , dopamine
Brain trauma was induced in mice using a closed head injury (CHI) model. At 1, 6 or 24 h after trauma, brains were dissected into the cortex, striatum and hippocampus. Changes in levels of processed X‐box protein 1 ( xbp1 ), glucose‐regulated protein 78 ( grp78 ), growth arrest and DNA damage‐inducible gene 153 ( gadd153 ) and heat‐shock protein 70 ( hsp70 ) mRNA, indicating impaired endoplasmic reticulum (ER) and cytoplasmic functioning, were evaluated by quantitative PCR. In the cortex, processed xbp1 mRNA levels rose to 2000% of control 1 h after CHI, and stayed high throughout the experiments. In the hippocampus and striatum, processed xbp1 mRNA levels rose in a delayed fashion, peaking at 6 h (1000% of control) and 24 h after CHI (1500% of control) respectively. Levels of g rp78 mRNA were only slightly increased in the cortex 24 h after CHI (150% of control), and were unchanged or transiently decreased in the hippocampus and striatum. Levels of g add153 mRNA did not change significantly after trauma. A transient rise in hsp70 mRNA levels was observed only in the cortex, peaking at 1 h after CHI (600% of control). Processing of xbp1 mRNA is a sign of activation of the unfolded protein response indicative of ER dysfunction. The results suggest that brain trauma induces ER dysfunction, which spreads from the ipsilateral cortex to the hippocampus and striatum. These observations may have clinical implications and should therefore be considered for future investigations on therapeutic intervention of brain injury caused by contusion‐induced neurotrauma.