RGD Reference Report - Immediate early gene induction after neonatal hypoxia-ischemia. - Rat Genome Database

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Immediate early gene induction after neonatal hypoxia-ischemia.

Authors: Gubits, RM  Burke, RE  Casey-McIntosh, G  Bandele, A  Munell, F 
Citation: Gubits RM, etal., Brain Res Mol Brain Res. 1993 May;18(3):228-38.
RGD ID: 2289081
Pubmed: PMID:7684483   (View Abstract at PubMed)

Immediate early gene (IEG) products, such as FOS and JUN, may partially mediate the long-term transcriptional response of CNS cells to specific changes in their environment. To determine whether IEG products might be involved in the immature brain's response to hypoxia-ischemia (H-I), 7-day-old rat pups were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia (8% O2/92% N2) at 37 degrees C, which results in pathological changes only in specific regions of the hemisphere ipsilateral to ligation. Time course experiments were performed, in which animals were sacrificed between 1 and 24 h after H-I. RNAs from several brain regions were analyzed by Northern blot hybridization for their relative concentrations of nine IEG mRNAs (c-fos, c-jun, junB, TIS 1 (nur77), TIS7, TIS8 (zif268), TIS10, TIS11, and TIS21). Induction of all IEGs, except TIS7 and TIS10, was observed in ipsilateral forebrain, and, less frequently, in contralateral forebrain, at 1, 2, and 3 h post-hypoxia. In some animals, lower levels of expression were also detected at 4, 18 and 24 h. With minor exceptions, co-induction of all seven IEGs was observed in a given RNA sample. Induction of two other mRNAs, representing the heat shock and astrocytic responses, were also observed. Hsp70 mRNA levels were increased only in the brains of animals exhibiting IEG induction. However, hsp70 induction was confined to the ipsilateral forebrain, implying a more direct relationship between its expression and permanent morphological damage. GFAP mRNA induction occurred predominantly in ipsilateral forebrain samples at 18 and 24 h post-hypoxia. Levels of B-actin and ubiquitin mRNAs were relatively constant in the same RNA samples. In control experiments c-fos mRNA induction was not detected after sham ligation with hypoxia, ligation with sham hypoxia, or hypoxia alone. These results suggest that the immature brain is highly responsive to H-I at the level of gene expression, involving at least three different rapid response systems.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Brain Hypoxia-Ischemia  ISOEgr1 (Rattus norvegicus)2289081; 2289081mRNA:increased expression:forebrain (rat)RGD 
Brain Hypoxia-Ischemia  IEP 2289081mRNA:increased expression:forebrain (rat)RGD 
brain ischemia  ISOBtg2 (Rattus norvegicus)2289081; 2289081mRNA:increased expression:forebrain (rat)RGD 
brain ischemia  IEP 2289081mRNA:increased expression:forebrain (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Btg2  (BTG anti-proliferation factor 2)
Egr1  (early growth response 1)

Genes (Mus musculus)
Btg2  (BTG anti-proliferation factor 2)
Egr1  (early growth response 1)

Genes (Homo sapiens)
BTG2  (BTG anti-proliferation factor 2)
EGR1  (early growth response 1)


Additional Information