PMID- 25600517 OWN - NLM STAT- MEDLINE DCOM- 20160810 LR - 20181113 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 12 DP - 2015 Jan 20 TI - Scutellarin regulates the Notch pathway and affects the migration and morphological transformation of activated microglia in experimentally induced cerebral ischemia in rats and in activated BV-2 microglia. PG - 11 LID - 10.1186/s12974-014-0226-z [doi] LID - 11 AB - BACKGROUND: Activated microglial cells release an excess of inflammatory mediators after an ischemic stroke. We reported previously that scutellarin effectively suppressed the inflammatory response induced by activated microglia in rats subjected to middle cerebral artery occlusion (MCAO); however, the mechanism via which scutellarin exerts its effects on microglial activation has not been explored. This study aimed to elucidate if scutellarin can regulate the Notch pathway that is linked to microglia activation in MCAO rat, and in lipopolysaccharide (LPS)-induced BV-2 microglia. Along with this, we also investigated some characteristic behavioral responses of activated microglia. METHODS: Expression of various members of the Notch pathway, including Notch-1, intracellular Notch receptor domain (NICD), recombining binding protein suppressor of hairless (RBP-JK) and transcription factor hairy and enhancer of split-1 (Hes-1) in activated microglia was assessed by immunofluorescence staining and western blot after experimental MCAO and in vitro LPS activation. The effect of scutellarin on migration of microglia was determined by the transwell chamber assay as well as expression of monocyte chemoattractant protein-1 (MCP-1). The morphological change of microglia induced by scutellarin was detected by F-actin staining and electron microscopy. RESULTS: Scutellarin markedly attenuated the expression of NF-kappaB, Notch-1, NICD, RBP-JK and Hes-1 both in vivo and in activated microglia. It decreased the expression of MCP-1 and microglial migration, but increased the ability of microglia adhesion. Scutellarin also altered the phenotype of microglia by causing rearrangement or reorganization of its cytoskeleton. CONCLUSIONS: The results suggest that scutellarin regulates the activation of microglia via the Notch pathway and concurrently induces morphological and functional changes in activated microglia. FAU - Yuan, Yun AU - Yuan Y AD - Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, PR China. yunyuankm@126.com. FAU - Rangarajan, Parakalan AU - Rangarajan P AD - Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore, 117597, Singapore. antpara@nus.edu.sg. FAU - Kan, Enci Mary AU - Kan EM AD - Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore, 117510, Singapore. kencimar@dso.org.sg. FAU - Wu, Yajun AU - Wu Y AD - Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore, 117597, Singapore. ya_jun_wu@nuhs.edu.sg. FAU - Wu, Chunyun AU - Wu C AD - Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, PR China. wuchunyunkm@163.com. FAU - Ling, Eng-Ang AU - Ling EA AD - Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore, 117597, Singapore. antlea@nus.edu.sg. LA - eng PT - Journal Article DEP - 20150120 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Actins) RN - 0 (Glucuronates) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Notch) RN - 0 (Tumor Necrosis Factor-alpha) RN - 16IGP0ML9A (scutellarin) RN - 7V515PI7F6 (Apigenin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Actins/metabolism MH - Animals MH - Apigenin/pharmacology/*therapeutic use MH - Cell Adhesion/drug effects MH - Cell Line, Transformed MH - Cell Movement/*drug effects MH - Cerebrum/drug effects/pathology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Glucuronates/pharmacology/*therapeutic use MH - Infarction, Middle Cerebral Artery/*drug therapy/*pathology MH - Lipopolysaccharides/pharmacology MH - Male MH - Microglia/drug effects/metabolism/ultrastructure MH - Nitric Oxide Synthase Type II/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Notch/*metabolism MH - Signal Transduction/*drug effects MH - Tumor Necrosis Factor-alpha/metabolism MH - rho GTP-Binding Proteins/metabolism PMC - PMC4316603 EDAT- 2015/01/21 06:00 MHDA- 2016/08/11 06:00 PMCR- 2015/01/20 CRDT- 2015/01/21 06:00 PHST- 2014/10/29 00:00 [received] PHST- 2014/12/19 00:00 [accepted] PHST- 2015/01/21 06:00 [entrez] PHST- 2015/01/21 06:00 [pubmed] PHST- 2016/08/11 06:00 [medline] PHST- 2015/01/20 00:00 [pmc-release] AID - s12974-014-0226-z [pii] AID - 226 [pii] AID - 10.1186/s12974-014-0226-z [doi] PST - epublish SO - J Neuroinflammation. 2015 Jan 20;12:11. doi: 10.1186/s12974-014-0226-z.