CD38 positively regulates postnatal development of astrocytes cell-autonomously and oligodendrocytes non-cell-autonomously

Tsuyoshi Hattori, Minoru Kaji, Hiroshi Ishii, Roboon Jureepon, Mika Takarada-Iemata, Hieu Minh Ta, Thuong Manh Le, Ayumu Konno, Hirokazu Hirai, Yoshitake Shiraishi, Noriyuki Ozaki, Yasuhiko Yamamoto, Hiroshi Okamoto, Shigeru Yokoyama, Haruhiro Higashida, Yasuko Kitao, Osamu Hori

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)974-989
Number of pages16
JournalGlia
Volume65
Issue number6
DOIs
Publication statusPublished - 2017 Jun

Keywords

  • NAD
  • autism
  • connexin 43
  • cortex
  • hemichannel
  • myelin

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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