title: Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain.
abstract: Phaseic acid (PA) is a phytohormone regulating important physiological functions in higher plants. Here, we show the presence of naturally occurring (-)-PA in mouse and rat brains. (-)-PA is exclusively present in the choroid plexus and the cerebral vascular endothelial cells. Purified (-)-PA has no toxicity and protects cultured cortical neurons against glutamate toxicity through reversible inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery elicited a significant induction in (-)-PA expression in the cerebrospinal fluid but not in the peripheral blood. Importantly, (-)-PA induction only occurred in the penumbra area, indicting a protective role of PA in the brain. Indeed, elevating the (-)-PA level in the brain reduced ischemic brain injury, whereas reducing the (-)-PA level using a monoclonal antibody against (-)-PA increased ischemic injury. Collectively, these studies showed for the first time that (-)-PA is an endogenous neuroprotective molecule capable of reversibly inhibiting glutamate receptors during ischemic brain injury.
authors.affiliation: From the Brain Research Centre and Department of Biology, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Nanshan District, Shenzhen, 518055 Guangdong Province, China, hou.st@sustc.edu.cn.|Experimental NeuroTherapeutics, Human Health Therapeutics Portfolio, National Research Council Canada, 1200 Montreal Road, Building M54, Ottawa K1A 0R6, Ontario, Canada.|the Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Sheng Tao
authors.initials: ST
authors.lastname: Hou
authors.affiliation: Experimental NeuroTherapeutics, Human Health Therapeutics Portfolio, National Research Council Canada, 1200 Montreal Road, Building M54, Ottawa K1A 0R6, Ontario, Canada.
authors.forename: Susan X
authors.initials: SX
authors.lastname: Jiang
authors.affiliation: Aquatic and Crop Resource Development, National Research Council Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan S7N 0W9, Canada, and.
authors.forename: L Irina
authors.initials: LI
authors.lastname: Zaharia
authors.affiliation: Aquatic and Crop Resource Development, National Research Council Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan S7N 0W9, Canada, and.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Han
authors.affiliation: Aquatic and Crop Resource Development, National Research Council Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan S7N 0W9, Canada, and.
authors.forename: Chantel L
authors.initials: CL
authors.lastname: Benson
authors.affiliation: Experimental NeuroTherapeutics, Human Health Therapeutics Portfolio, National Research Council Canada, 1200 Montreal Road, Building M54, Ottawa K1A 0R6, Ontario, Canada.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Slinn
authors.affiliation: Aquatic and Crop Resource Development, National Research Council Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan S7N 0W9, Canada, and.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Abrams
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D012717:Sesquiterpenes; C000612858:phaseic acid; D018698:Glutamic Acid
keywords: UPLC/MS/MS; abscisic acid (ABA); cerebral ischemia; choroid plexus; endothelial cells; neurochemistry; neurological disease; neuroprotection; phaseic acid; stroke