Overexpression of Spexin 1 in the Dorsal Habenula Reduces Anxiety in Zebrafish

Overview

Journal Front Neural Circuits

Date 2019 Sep 3

PMID 31474838

Citations 16

Authors

Inyoung Jeong

Eunmi Kim

Jae Young Seong

Hae-Chul Park

Affiliations

Soon will be listed here.

Abstract

Spexin (SPX) is an evolutionarily conserved neuropeptide that is expressed in the mammalian brain and peripheral tissue. Two orthologs are present in the teleost, SPX1 and SPX2. SPX1 is involved in reproduction and food intake. Recently, SPX1 neurons have been found to be located in the specific nuclei of dorsal habenula (dHb) and to project into the interpeduncular nucleus (IPN), in which galanin receptor 2a/2b (GALR2a/2b) expression was also observed. This indicates that habenula SPX1 neurons may interact with GALR2a/2b in the IPN; however, the function of SPX1 in the dHb-IPN neuronal circuit remains unknown. To determine the role of SPX1 in the dHb-IPN neural circuit, we generated transgenic zebrafish overexpressing SPX1 specifically in the dHb. We found that transgenic zebrafish overexpressing SPX1 in the dHb had anxiolytic behaviors compared with their wildtype siblings. Furthermore, quantitative PCR revealed that mRNA expression of and in the IPN and serotonin-related genes in the raphe was upregulated in the brains of transgenic zebrafish. Taken together, our data suggest that SPX1 function in the dHb-IPN neural circuits is implicated in the regulation of anxiety behaviors modulation of the serotoninergic system in zebrafish.

Citing Articles

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References

Mirabeau O, Perlas E, Severini C, Audero E, Gascuel O, Possenti R . Identification of novel peptide hormones in the human proteome by hidden Markov model screening. Genome Res. 2007; 17(3):320-7. PMC: 1800923. DOI: 10.1101/gr.5755407. View

Amo R, Aizawa H, Takahoko M, Kobayashi M, Takahashi R, Aoki T . Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula. J Neurosci. 2010; 30(4):1566-74. PMC: 6633804. DOI: 10.1523/JNEUROSCI.3690-09.2010. View

Broms J, Antolin-Fontes B, Tingstrom A, Ibanez-Tallon I . Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates. J Comp Neurol. 2014; 523(3):359-80. PMC: 4270839. DOI: 10.1002/cne.23664. View

Kim E, Jeong I, Chung A, Kim S, Kwon S, Seong J . Distribution and neuronal circuit of spexin 1/2 neurons in the zebrafish CNS. Sci Rep. 2019; 9(1):5025. PMC: 6430828. DOI: 10.1038/s41598-019-41431-7. View

Yamaguchi T, Danjo T, Pastan I, Hikida T, Nakanishi S . Distinct roles of segregated transmission of the septo-habenular pathway in anxiety and fear. Neuron. 2013; 78(3):537-44. PMC: 3654012. DOI: 10.1016/j.neuron.2013.02.035. View

Wong M, Sze K, Chen T, Cho C, Law H, Chu I . Goldfish spexin: solution structure and novel function as a satiety factor in feeding control. Am J Physiol Endocrinol Metab. 2013; 305(3):E348-66. DOI: 10.1152/ajpendo.00141.2013. View

ODonnell D, Ahmad S, Wahlestedt C, Walker P . Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. J Comp Neurol. 1999; 409(3):469-81. View

Lv S, Cui B, Yang Y, Du H, Zhang X, Zhou Y . Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model. Am J Pathol. 2019; 189(4):886-899. DOI: 10.1016/j.ajpath.2018.12.009. View

Hsu Y, Morton G, Guy E, Wang S, Turner E . Dorsal Medial Habenula Regulation of Mood-Related Behaviors and Primary Reinforcement by Tachykinin-Expressing Habenula Neurons. eNeuro. 2016; 3(3). PMC: 4947983. DOI: 10.1523/ENEURO.0109-16.2016. View

10.

Ma A, Bai J, He M, Wong A . Spexin as a neuroendocrine signal with emerging functions. Gen Comp Endocrinol. 2018; 265:90-96. DOI: 10.1016/j.ygcen.2018.01.015. View

11.

Kim J, Lee S, Li L, Park H, Park J, Lee K . High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One. 2011; 6(4):e18556. PMC: 3084703. DOI: 10.1371/journal.pone.0018556. View

12.

Hikosaka O . The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci. 2010; 11(7):503-13. PMC: 3447364. DOI: 10.1038/nrn2866. View

13.

Liu Y, Li S, Qi X, Zhou W, Liu X, Lin H . A novel neuropeptide in suppressing luteinizing hormone release in goldfish, Carassius auratus. Mol Cell Endocrinol. 2013; 374(1-2):65-72. DOI: 10.1016/j.mce.2013.04.008. View

14.

Toll L, Khroyan T, Sonmez K, Ozawa A, Lindberg I, McLaughlin J . Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception. FASEB J. 2011; 26(2):947-54. PMC: 3290442. DOI: 10.1096/fj.11-192831. View

15.

Reyes-Alcaraz A, Lee Y, Son G, Kim N, Kim D, Yun S . Development of Spexin-based Human Galanin Receptor Type II-Specific Agonists with Increased Stability in Serum and Anxiolytic Effect in Mice. Sci Rep. 2016; 6:21453. PMC: 4764904. DOI: 10.1038/srep21453. View

16.

Porzionato A, Rucinski M, Macchi V, Stecco C, Malendowicz L, De Caro R . Spexin expression in normal rat tissues. J Histochem Cytochem. 2010; 58(9):825-37. PMC: 2924798. DOI: 10.1369/jhc.2010.956300. View

17.

Mathuru A, Jesuthasan S . The medial habenula as a regulator of anxiety in adult zebrafish. Front Neural Circuits. 2013; 7:99. PMC: 3664309. DOI: 10.3389/fncir.2013.00099. View

18.

Brunner S, Farzi A, Locker F, Holub B, Drexel M, Reichmann F . GAL3 receptor KO mice exhibit an anxiety-like phenotype. Proc Natl Acad Sci U S A. 2014; 111(19):7138-43. PMC: 4024886. DOI: 10.1073/pnas.1318066111. View

19.

Okamoto H, Agetsuma M, Aizawa H . Genetic dissection of the zebrafish habenula, a possible switching board for selection of behavioral strategy to cope with fear and anxiety. Dev Neurobiol. 2011; 72(3):386-94. DOI: 10.1002/dneu.20913. View

20.

Thisse C, Thisse B . High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc. 2008; 3(1):59-69. DOI: 10.1038/nprot.2007.514. View