title: CD38 positively regulates postnatal development of astrocytes cell-autonomously and oligodendrocytes non-cell-autonomously.
abstract: Glial development is critical for the function of the central nervous system. CD38 is a multifunctional molecule with ADP-ribosyl cyclase activity. While critical roles of CD38 in the adult brain such as oxytocin release and social behavior have been reported, those in the developing brain remain largely unknown. Here we demonstrate that deletion of Cd38 leads to impaired development of astrocytes and oligodendrocytes in mice. CD38 is highly expressed in the developing brains between postnatal day 14 (P14) and day 28 (P28). In situ hybridization and FACS analysis revealed that CD38 is expressed predominantly in astrocytes in these periods. Analyses of the cortex of Cd38 knockout (Cd38-/-) mice revealed delayed development of astrocytes and subsequently delayed differentiation of oligodendrocytes (OLs) at postnatal stages. In vitro experiments using primary OL cultures, mixed glial cultures, and astrocytic conditioned medium showed that astrocytic CD38 regulates the development of astrocytes in a cell-autonomous manner and the differentiation of OLs in a non-cell-autonomous manner. Further experiments revealed that connexin43 (Cx43) in astrocytes plays a promotive role for CD38-mediated OL differentiation. Finally, increased levels of NAD+, caused by CD38 deficiency, are likely to be responsible for the suppression of astrocytic Cx43 expression and OL differentiation. Our data indicate that CD38 is a positive regulator of astrocyte and OL development.
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Tsuyoshi
authors.identifier: 0000-0002-8168-8710
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kaji
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Roboon
authors.initials: R
authors.lastname: Jureepon
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takarada-Iemata
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hieu
authors.initials: H
authors.lastname: Minh Ta
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Thuong
authors.initials: T
authors.lastname: Manh Le
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Konno
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Department of Functional Anatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Department of Functional Anatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ozaki
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.|Department of Biochemistry, Tohoku University, Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kitao
authors.affiliation: Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Osamu
authors.identifier: 0000-0002-2210-0446
authors.initials: O
authors.lastname: Hori
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018031:Connexin 43 / Q000378:metabolism; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009243:NAD / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; D008562:Membrane Glycoproteins; D009243:NAD; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; C498156:Cd38 protein, rat; D051997:ADP-ribosyl Cyclase 1
keywords: NAD; autism; connexin 43; cortex; hemichannel; myelin