PMID- 23415676 OWN - NLM STAT- MEDLINE DCOM- 20130826 LR - 20130318 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1504 DP - 2013 Apr 4 TI - Effects of moderate and deep hypothermia on RNA-binding proteins RBM3 and CIRP expressions in murine hippocampal brain slices. PG - 74-84 LID - S0006-8993(13)00137-6 [pii] LID - 10.1016/j.brainres.2013.01.041 [doi] AB - Therapeutic hypothermia has emerged as an effective neuroprotective therapy for cardiac arrest survivors. There are a number of purported mechanisms for therapeutic hypothermia, but the exact mechanism still remains to be elucidated. Although hypothermia generally down-regulates protein synthesis and metabolism in mammalian cells, a small subset of homologous (>70%) cold-shock proteins (RNA-binding motif protein 3, RBM3 and cold-inducible RNA-binding protein, CIRP) are induced under these conditions. In addition, RBM3 up-regulation in neuronal cells has recently been implicated in hypothermia-induced neuroprotection. Therefore, we compared the effects of moderate (33.5 degrees C) and deep (17 degrees C) hypothermia with normothermia (37 degrees C) on the regulation of RBM3 and CIRP expressions in murine organotypic hippocampal slice cultures (OHSC), hippocampal neuronal cells (HT-22), and microglia cells (BV-2). Moderate hypothermia resulted in significant up-regulation of both RBM3 and CIRP mRNA in murine OHSC, but deep hyporthermia did not. RBM3 protein regulation was also significantly up-regulated by 33.5 degrees C, but no significant up-regulation of CIRP protein was observed in the OHSC. Additionally, OHSC exposed to 17 degrees C for 24h were positive for Propidium Iodide (PI) immunostaining, indicating the onset of cell death. Similarly, RBM3 gene expression in a HT-22 neuronal cells mono-culture and direct co-culture of HT-22 neuronal cells with BV-2 microglia cells were also up-regulated at 33.5 degrees C but only in the co-culture at 17 degrees C. No significant up-regulation of RBM3 nor CIRP gene expression were observed in a BV-2 mono-culture at either temperature. We observed that RBM3 mRNA and protein expressions in murine OHSC, as well as in mono-culture of HT-22 neuronal cells and direct co-culture of HT-22 neuronal cells with BV-2 microglia cells were significantly up-regulated by exposure to moderate hypothermia. These findings further support the implication of RBM3 as a potential effector for hypothermia-induced neuroprotection. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Tong, Giang AU - Tong G AD - Department of Congenital Heart Disease/Pediatric Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. giang.tong@charite.de FAU - Endersfelder, Stefanie AU - Endersfelder S FAU - Rosenthal, Lisa-Maria AU - Rosenthal LM FAU - Wollersheim, Sonja AU - Wollersheim S FAU - Sauer, Igor Maximilian AU - Sauer IM FAU - Buhrer, Christoph AU - Buhrer C FAU - Berger, Felix AU - Berger F FAU - Schmitt, Katharina Rose Luise AU - Schmitt KR LA - eng PT - Journal Article DEP - 20130208 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Cirbp protein, mouse) RN - 0 (RNA-Binding Proteins) RN - 0 (Rbm3 protein, mouse) SB - IM MH - Animals MH - Cell Line MH - Coculture Techniques MH - Hippocampus/*metabolism MH - *Hypothermia, Induced MH - Immunoblotting MH - Mice MH - Mice, Inbred C57BL MH - Microglia/metabolism MH - Neurons/metabolism MH - Organ Culture Techniques MH - RNA-Binding Proteins/*biosynthesis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Up-Regulation EDAT- 2013/02/19 06:00 MHDA- 2013/08/27 06:00 CRDT- 2013/02/19 06:00 PHST- 2012/08/07 00:00 [received] PHST- 2013/01/02 00:00 [revised] PHST- 2013/01/22 00:00 [accepted] PHST- 2013/02/19 06:00 [entrez] PHST- 2013/02/19 06:00 [pubmed] PHST- 2013/08/27 06:00 [medline] AID - S0006-8993(13)00137-6 [pii] AID - 10.1016/j.brainres.2013.01.041 [doi] PST - ppublish SO - Brain Res. 2013 Apr 4;1504:74-84. doi: 10.1016/j.brainres.2013.01.041. Epub 2013 Feb 8.