title: Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses.
abstract: Lysophosphatidic acid (LPA) is one of the well-characterized, ubiquitous phospholipid molecules. LPA exerts its effect by activating G protein-coupled receptors known as LPA receptors (LPARs). So far, LPAR signaling has been critically implicated during early development stages, including the regulation of synapse formation and the morphology of cortical and hippocampal neurons. In adult brains, LPARs seem to participate in cognitive as well as emotional learning and memory. Recent studies using LPAR1-deficient mice reported impaired performances in a number of behavioral tasks, including the hippocampus-dependent spatial memory and fear conditioning tests. Nevertheless, the effect of LPAR activation in the synaptic transmission of central synapses after the completion of embryonic development has not been investigated. In this study, we took advantage of a novel extracellular agonist for LPARs called gintonin to activate LPARs in adult brain systems. Gintonin, a recently identified active ingredient in ginseng, has been shown to activate LPARs and mobilize Ca(2+) in an artificial cell system. We found that the activation of LPARs by application of gintonin acutely enhanced both excitatory and inhibitory transmission in central synapses, albeit through tentatively distinct mechanisms. Gintonin-mediated LPAR activation primarily resulted in synaptic enhancement and an increase in neuronal excitability in a phospholipase C-dependent manner. Our findings suggest that LPARs are able to directly potentiate synaptic transmission in central synapses when stimulated exogenously. Therefore, LPARs could serve as a useful target to modulate synaptic activity under pathological conditions, including neurodegenerative diseases.
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea; and.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea; and.
authors.forename: Sungmin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea; and.
authors.forename: Jeehae
authors.initials: J
authors.lastname: Rhee
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea; and.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea; and cchung@konkuk.ac.kr.
authors.forename: ChiHye
authors.initials: C
authors.lastname: Chung
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D049368:Receptors, Lysophosphatidic Acid; C000603040:gintonin; D010738:Type C Phospholipases; D002118:Calcium
keywords: ginseng; gintonin; lysophosphatidic acid receptor; synaptic potentiation