title: mRNA redistribution during permanent focal cerebral ischemia.
abstract: Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not 40S or 60S ribosomal subunits, or organelle markers. The volume of brain with mRNA granule-containing neurons decreased exponentially with ischemia duration, and was zero after 8 h permanent focal cerebral ischemia or any duration of ischemia in diabetic rats. These results show that neuronal mRNA granule response has a limited range of insult intensity over which it is expressed. Identifying the limits of effective neuronal stress response to ischemia will be important for developing effective stroke therapies.
authors: Department of Physiology, Wayne State University School of Medicine, 4116 Scott Hall, 540 East Canfield Ave, Detroit, MI, 48201, USA.
authors: Monique K
authors: MK
authors: Lewis
authors: Jill T
authors: JT
authors: Jamison
authors: Joseph C
authors: JC
authors: Dunbar
authors: Donald J
authors: DJ
authors: DeGracia
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism; D013997:Time Factors
chemical_list: D034961:Antigens, Nuclear; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; C546339:Rbfox3 protein, rat