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CD38 positively regulates postnatal development of astrocytes cell‐autonomously and oligodendrocytes non‐cell‐autonomously
Author(s) -
Hattori Tsuyoshi,
Kaji Minoru,
Ishii Hiroshi,
Jureepon Roboon,
TakaradaIemata Mika,
Minh Ta Hieu,
Manh Le Thuong,
Konno Ayumu,
Hirai Hirokazu,
Shiraishi Yoshitake,
Ozaki Noriyuki,
Yamamoto Yasuhiko,
Okamoto Hiroshi,
Yokoyama Shigeru,
Higashida Haruhiro,
Kitao Yasuko,
Hori Osamu
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23139
Subject(s) - biology , cd38 , astrocyte , microbiology and biotechnology , neuroscience , oligodendrocyte , neuroglia , central nervous system , in situ hybridization , gene expression , biochemistry , myelin , stem cell , gene , cd34
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.