title: Galacto-N-biose is neuroprotective against glutamate-induced excitotoxicity in vitro.
abstract: Galacto-N-biose (GNB: Galβ1-3GalNAc) is an O-glycan disaccharide core moiety that is a core component of mucin in the gastrointestinal tract; however, the physiological properties of GNB are not well understood. Glutamate excitotoxicity causes neuronal death in acute neurological disorders including stroke, trauma, and neurodegenerative disease. Therefore the discovery of drugs to treat glutamate excitotoxicity is an important goal. Here, we report that GNB is neuroprotective against glutamate-induced excitotoxicity. We treated 14-15 days in vitro cultured rat cortical neurons with 0.1-1000nM GNB together with 30µm glutamate for various durations. Short-term (3h) GNB treatments showed a modest neuroprotective effect against glutamate neurotoxicity, however, long-term (24h) GNB treatment conferred significant neuroprotective effects, as shown by both MTT and immunocytochemical assays. Prolonged GNB treatment did not alter glutamate-induced calcium influx, but did induce antioxidant-related gene expression. Furthermore, GNB treatment did not induce cell death or alter synaptic connections. These data suggest that GNB is a potential candidate drug that protects against glutamate excitotoxicity without affecting cell viability and synaptic connections.
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan. Electronic address: yshinoda-ns@umin.net.
authors.forename: Yo
authors.initials: Y
authors.lastname: Shinoda
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Iguchi
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tatsumi
authors.affiliation: Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-8642, Japan.
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Kitaoka
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan. Electronic address: tfuruichi@rs.tus.ac.jp.
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004186:Disaccharidases / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004187:Disaccharides; D018696:Neuroprotective Agents; D009498:Neurotoxins; C000616516:galacto-N-biose; D018698:Glutamic Acid; D004186:Disaccharidases
keywords: Cortical neuron; Excitotoxicity; GNB; Glutamate