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Cyclic ADP-Ribose and Heat Regulate Oxytocin Release via CD38 and TRPM2 in the Hypothalamus

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Neurosecretion: Secretory Mechanisms

Part of the book series: Masterclass in Neuroendocrinology ((MANEURO,volume 8))

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Abstract

Oxytocin (OT) is a critical molecule for social recognition that mediates social memory and emotional behaviors. OT is known to be released during stress and acts as an anxiolytic factor. Recent studies revealed higher levels of OT release in hypothalamus culture isolated from subordinate mice in group-housed males than in that from dominant mice after cage-switch stress. OT concentrations in micro-perfusates at the paraventricular nucleus upon perfusion stimulation with cADPR were enhanced in subordinate mice compared with dominant mice. OT concentration in cerebrospinal fluid was higher in endotoxin-shock mice with fever than in controls without an increase in body temperature. In mice exposed to the new environmental stress, the CSF OT level transiently increased at 5 min from start of exposure, while the rectal temperature also increased. OT release under various conditions was sensitive to antagonists, gene knockout, or mRNA levels of CD38 or TRPM2 in the hypothalamus. These findings indicated that cADPR and hyperthermia co-regulate hypothalamic OT secretion during social stress by elevation of intracellular free Ca2+ concentrations involved in CD38-dependent Ca2+ mobilization and TRPM2-dependent Ca2+ influx. Interaction between CD38 and TRPM2 seems to involve a different mechanism for stress-induced release of OT that may result in anxiolytic effects, resulting in transient rescission of autistic phenotypes.

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Author information

Authors and Affiliations

  1. Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan

    Haruhiro Higashida & Olga Lopatina

Authors
  1. Haruhiro Higashida
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  2. Olga Lopatina
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Corresponding author

Correspondence to Haruhiro Higashida .

Editor information

Editors and Affiliations

  1. Medical School, University of Massachusetts, Worcester, MA, USA

    José R. Lemos

  2. Molecular Mechanisms in Neurodegenerative Diseases Laboratory, MMDN, University of Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, France

    Govindan Dayanithi

Key References: See Main List for Reference Details

Key References: See Main List for Reference Details

  • Higashida et al. (2017) This article stresses the relation between hyperthermia and autism or stress.

  • Jin et al. (2007) This is the first paper to describe the role of CD38 and its product, cyclic ADP-ribose, in social behavior.

  • Liu et al. (2012) The article shows oxytocin release owing to heat in vitro.

  • Munesue et al. (2016) In this clinical trial, it is reported that patients with both autism spectrum disorder and intellectual disability were feasible to oxytocin nasal administration.

  • Naviaux et al. (2017) This article describes that suramin is used for treatment of autism by hyperthermia.

  • Zhong et al. (2016) This paper describes that oxytocin release in the brain is owing to both hyperthermia and cyclic ADP-ribose in subordinate mice exposed to social stress.

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Higashida, H., Lopatina, O. (2020). Cyclic ADP-Ribose and Heat Regulate Oxytocin Release via CD38 and TRPM2 in the Hypothalamus. In: Lemos, J., Dayanithi, G. (eds) Neurosecretion: Secretory Mechanisms. Masterclass in Neuroendocrinology, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-030-22989-4_3

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