title: Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage.
abstract: Oligodendrocyte precursor cells (OPCs) undergo a series of energy-consuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca(2+) elevation in OPCs, indicating a Ca(2+)-dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energy-metabolism-directed oligodendroglial-targeted therapies.
authors.affiliation: Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Institut National de la Santé et de la Recherche Médicale U1050, Paris 75231, Cedex 05, France.
authors.forename: Chenju
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Huang
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Institut National de la Santé et de la Recherche Médicale U1050, Paris 75231, Cedex 05, France.
authors.forename: Annette
authors.initials: A
authors.lastname: Koulakoff
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chuanhuang
authors.initials: C
authors.lastname: Weng
authors.affiliation: Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chengren
authors.initials: C
authors.lastname: Li
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Cong-Jian
authors.initials: CJ
authors.lastname: Zhao
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Institut National de la Santé et de la Recherche Médicale U1050, Paris 75231, Cedex 05, France christian.giaume@college-de-france.fr xiaolan35@tmmu.edu.cn.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
authors.affiliation: Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China christian.giaume@college-de-france.fr xiaolan35@tmmu.edu.cn.
authors.forename: Lan
authors.identifier: 0000-0002-0391-6909
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003337:Corpus Callosum / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; D005947:Glucose; D002118:Calcium
keywords: Connexin hemichannel; Glial metabolism; Glucose uptake; Intracellular Ca2+; Oligodendroglia