A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System

• Published in: iScience Vol. 23; no. 3; p. 100921
• Main Authors: Farkas, Erzsébet, Varga, Edina, Kovács, Balázs, Szilvásy-Szabó, Anett, Cote-Vélez, Antonieta, Péterfi, Zoltán, Matziari, Magdalini, Tóth, Mónika, Zelena, Dóra, Mezriczky, Zsolt, Kádár, Andrea, Kővári, Dóra, Watanabe, Masahiko, Kano, Masanobu, Mackie, Ken, Rózsa, Balázs, Ruska, Yvette, Tóth, Blanka, Máté, Zoltán, Erdélyi, Ferenc, Szabó, Gábor, Gereben, Balázs, Lechan, Ronald M., Charli, Jean-Louis, Joseph-Bravo, Patricia, Fekete, Csaba
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27-03-2020; Elsevier
• Subjects: Molecular Physiology; Neuroanatomy; Neuroscience; Molecular Physiology; Neuroscience; Neuroanatomy
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.100921

Based on the type-I cannabinoid receptor (CB1) content of hypophysiotropic axons and the involvement of tanycytes in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis, we hypothesized that endocannabinoids are involved in the tanycyte-induced regulation of TRH release in the median eminence (ME). We demonstrated that CB1-immunoreactive TRH axons were associated to DAGLα-immunoreactive tanycyte processes in the external zone of ME and showed that endocannabinoids tonically inhibit the TRH release in this tissue. We showed that glutamate depolarizes the tanycytes, increases their intracellular Ca2+ level and the 2-AG level of the ME via AMPA and kainite receptors and glutamate transport. Using optogenetics, we demonstrated that glutamate released from TRH neurons influences the tanycytes in the ME.
In summary, tanycytes regulate TRH secretion in the ME via endocannabinoid release, whereas TRH axons regulate tanycytes by glutamate, suggesting the existence of a reciprocal microcircuit between tanycytes and TRH terminals that controls TRH release.
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•Tanycytes tonically inhibit the activity of TRH axons via endocannabinoid release•Glutamate depolarizes the tanycytes and regulates their 2-AG synthesis•Glutamate released from the hypophysiotropic TRH axons influences tanycytes•A microcircuit utilizing glutamate and endocannabinoids regulates TRH release
Molecular Physiology; Neuroscience; Neuroanatomy