期刊
ISCIENCE
卷 23, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2020.100921
关键词
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资金
- Hungarian Science Foundation [OTKA K109710]
- Hungarian National Brain Research Program [2017-1.2.1-NKP-2017-00002]
- EU H2020 THYRAGE [666869]
- CONACYT-Mexico [CB2015/254960, ERC682426, KFI-2016-0177, GINOP-2016-00979, NVKP-2016-0043]
- BME-Biotechnology FIKP grant of EMMI (BME FIKP-BIO)
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 DAGL alpha-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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