Neurotensin Enhances Locomotor Activity and Arousal and Inhibits Melanin-Concentrating Hormone Signaling

Talia Levitas-Djerbi, Dana Sagi, Ilana Lebenthal-Loinger, Tali Lerer-Goldshtein, Lior Appelbaum

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Hypothalamic neurotensin (Nts)-secreting neurons regulate fundamental physiological processes including metabolism and feeding. However, the role of Nts in modulation of locomotor activity, sleep, and arousal is unclear. We previously identified and characterized Nts neurons in the zebrafish hypothalamus. Materials and Methods: In order to study the role of Nts, nts mutant (nts-/-), and overexpressing zebrafish were generated. Results: The expression of both nts mRNA and Nts protein was reduced during the night in wild-type zebrafish. Behavioral assays revealed that locomotor activity was decreased during both day and night, while sleep was increased exclusively during the nighttime in nts-/- larvae. Likewise, inducible overexpression of Nts increased arousal in hsp70:Gal4/uas:Nts larvae. Furthermore, the behavioral response to light-to-dark transitions was reduced in nts-/- larvae. In order to elucidate potential contenders that may mediate Nts action on these behaviors, we profiled the transcriptome of 6 dpf nts-/- larvae. Among other genes, the expression levels of melanin-concentrating hormone receptor 1b were increased in nts-/- larvae. Furthermore, a portion of promelanin-concentrating hormone 1 (pmch1) and pmch2 neurons expressed the nts receptor. In addition, expression of the the two zebrafish melanin-concentrating hormone (Mch) orthologs, Mch1 and Mch2, was increased in nts-/- larvae. Conclusion: These results show that the Nts and Mch systems interact and modulate locomotor activity and arousal.

Original languageEnglish
Pages (from-to)35-49
Number of pages15
JournalNeuroendocrinology
Volume110
Issue number1-2
DOIs
StatePublished - 1 Jan 2020

Bibliographical note

Publisher Copyright:
© 2019 S. Karger AG, Basel. Copyright: All rights reserved.

Funding

This work was supported by the US-Israel Binational Science Foundation (BSF, grants no. 2017105) and the Israel Science Foundation (Grant No. 690/15).

FundersFunder number
US-Israel Binational Science Foundation
United States-Israel Binational Science Foundation2017105
Israel Science Foundation690/15

    Keywords

    • Arousal
    • Melanin-concentrating hormone
    • Neurotensin
    • Sleep
    • Transcriptome
    • Zebrafish

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