Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory

Article26 June 2023 Source DataTransparent process Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory Tsuyoshi Hattori Corresponding Author Tsuyoshi Hattori [email protected] orcid.org/0000-0002-8168-8710 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Conceptualization, Formal analysis, ​Investigation, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Stanislav M Cherepanov Stanislav M Cherepanov Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation, Writing - original draft Search for more papers by this author Ryo Sakaga Ryo Sakaga Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Jureepon Roboon Jureepon Roboon orcid.org/0000-0001-6168-0351 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Dinh Thi Nguyen Dinh Thi Nguyen Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Hiroshi Ishii Hiroshi Ishii orcid.org/0000-0001-6776-4660 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Mika Takarada-Iemata Mika Takarada-Iemata orcid.org/0000-0002-2113-0707 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Takumi Nishiuchi Takumi Nishiuchi Division of Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation, Writing - original draft Search for more papers by this author Takayuki Kannon Takayuki Kannon orcid.org/0000-0001-9866-1621 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Kazuyoshi Hosomichi Kazuyoshi Hosomichi orcid.org/0000-0003-2712-1825 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Atsushi Tajima Atsushi Tajima orcid.org/0000-0001-6808-5491 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Yasuhiko Yamamoto Yasuhiko Yamamoto Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Resources Search for more papers by this author Hiroshi Okamoto Hiroshi Okamoto Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan Contribution: Resources Search for more papers by this author Akira Sugawara Akira Sugawara orcid.org/0000-0003-4511-8101 Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan Contribution: Resources Search for more papers by this author Haruhiro Higashida Haruhiro Higashida Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Contribution: Resources, Writing - original draft Search for more papers by this author Osamu Hori Osamu Hori orcid.org/0000-0002-2210-0446 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Resources, Writing - original draft Search for more papers by this author Tsuyoshi Hattori Corresponding Author Tsuyoshi Hattori [email protected] orcid.org/0000-0002-8168-8710 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Conceptualization, Formal analysis, ​Investigation, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Stanislav M Cherepanov Stanislav M Cherepanov Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation, Writing - original draft Search for more papers by this author Ryo Sakaga Ryo Sakaga Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Jureepon Roboon Jureepon Roboon orcid.org/0000-0001-6168-0351 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Dinh Thi Nguyen Dinh Thi Nguyen Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Hiroshi Ishii Hiroshi Ishii orcid.org/0000-0001-6776-4660 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Mika Takarada-Iemata Mika Takarada-Iemata orcid.org/0000-0002-2113-0707 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation Search for more papers by this author Takumi Nishiuchi Takumi Nishiuchi Division of Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan Contribution: ​Investigation, Writing - original draft Search for more papers by this author Takayuki Kannon Takayuki Kannon orcid.org/0000-0001-9866-1621 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Kazuyoshi Hosomichi Kazuyoshi Hosomichi orcid.org/0000-0003-2712-1825 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Atsushi Tajima Atsushi Tajima orcid.org/0000-0001-6808-5491 Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Formal analysis, ​Investigation Search for more papers by this author Yasuhiko Yamamoto Yasuhiko Yamamoto Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Resources Search for more papers by this author Hiroshi Okamoto Hiroshi Okamoto Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan Contribution: Resources Search for more papers by this author Akira Sugawara Akira Sugawara orcid.org/0000-0003-4511-8101 Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan Contribution: Resources Search for more papers by this author Haruhiro Higashida Haruhiro Higashida Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Contribution: Resources, Writing - original draft Search for more papers by this author Osamu Hori Osamu Hori orcid.org/0000-0002-2210-0446 Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Contribution: Resources, Writing - original draft Search for more papers by this author Author Information Tsuyoshi Hattori *,1, Stanislav M Cherepanov2, Ryo Sakaga1, Jureepon Roboon1, Dinh Thi Nguyen1, Hiroshi Ishii1, Mika Takarada-Iemata1, Takumi Nishiuchi3, Takayuki Kannon4, Kazuyoshi Hosomichi4, Atsushi Tajima4, Yasuhiko Yamamoto5, Hiroshi Okamoto5,6, Akira Sugawara7, Haruhiro Higashida2 and Osamu Hori1 1Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan 2Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan 3Division of Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan 4Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan 5Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan 6Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan 7Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan *Corresponding author. Tel: +81 76 265 2162; Fax: +81 76 234 4222; E-mail: [email protected] The EMBO Journal (2023)42:e111247https://doi.org/10.15252/embj.2022111247 Full textView the full text of the articlePDFDownload PDF of article text and main figures.PDF PLUSDownload PDF of article text, main figures, expanded view figures and appendix. Peer ReviewDownload a summary of the editorial decision process including editorial decision letters, reviewer comments and author responses to feedback. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP–ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults. Synopsis Postnatal expression of the ADP-ribosyl cyclase CD38 in astrocytes regulates neuronal circuit formation and social behavior in adults. Postnatal expression, but not adult expression, of CD38 in astrocytes regulates social memory. Astrocytic CD38 promotes excitatory synapse formation in the medial prefrontal cortex and hippocampal CA1 and CA2. Astrocytic CD38 promotes secretion of the synaptogenic protein SPARCL1 via cyclic ADP–ribose and calcium signaling. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 42,Issue 15,1 August 2023This cover highlights the article Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines by Gautier M. Courbon, John L. Rubinstein and colleagues. High‐resolution electron cryomicroscopy provides structural insight into the mode of action of two new tuberculosis drugs. 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