title: Complement Peptide C3a Promotes Astrocyte Survival in Response to Ischemic Stress.
abstract: Astrocytes are the most numerous cells in the central nervous system with a range of homeostatic and regulatory functions. Under normal conditions as well as after ischemia, astrocytes promote neuronal survival. We have previously reported that the complement-derived peptide C3a stimulates neuronal differentiation of neural progenitor cells and protects the immature brain tissue against hypoxic-ischemic injury. Here, we studied the effects of C3a on the response of mouse cortical astrocytes to ischemia. We have found that chemical ischemia, induced by combined inhibition of oxidative phosphorylation and glycolysis, upregulates the expression of C3a receptor in cultured primary astrocytes. C3a treatment protected wild-type but not C3a receptor-deficient astrocytes from cell death induced by chemical ischemia or oxygen-glucose deprivation by reducing ERK signaling and caspase-3 activation. C3a attenuated ischemia-induced upregulation of glial fibrillary acidic protein; however, the protective effects of C3a were not dependent on the presence of the astrocyte intermediate filament system. Pre-treatment of astrocytes with C3a during recovery abrogated the ischemia-induced neuroprotective phenotype of astrocytes. Jointly, these results provide the first evidence that the complement peptide C3a modulates the response of astrocytes to ischemia and increases their ability to cope with ischemic stress.
authors.affiliation: Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 440, 405 30, Gothenburg, Sweden.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shinjyo
authors.affiliation: Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 440, 405 30, Gothenburg, Sweden.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Pablo
authors.affiliation: Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 440, 405 30, Gothenburg, Sweden. milos.pekny@neuro.gu.se.|Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. milos.pekny@neuro.gu.se.|University of Newcastle, Newcastle, NSW, Australia. milos.pekny@neuro.gu.se.
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
authors.affiliation: Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 440, 405 30, Gothenburg, Sweden. marcela.pekna@neuro.gu.se.|Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. marcela.pekna@neuro.gu.se.|University of Newcastle, Newcastle, NSW, Australia. marcela.pekna@neuro.gu.se.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D018920:Coculture Techniques; D015926:Complement C3a / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D007382:Intermediate Filaments / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a; D020932:Nerve Growth Factor; D053148:Caspase 3
keywords: Caspase-3; Glial fibrillary acidic protein; Neuroprotection