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 galr2a and galr2b 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 via modulation of the serotoninergic system in zebrafish.
Highlights
Spexin is a secreted neuropeptide that is mainly expressed in the brain, pancreas, kidney, liver, ovary, and adrenal glands of mammals and fish (Mirabeau et al, 2007; Sonmez et al, 2009; Porzionato et al, 2010; Rucinski et al, 2010; Liu et al, 2013; Wong et al, 2013)
We previously demonstrated that spx1 is expressed in the specific nuclei of dorsal habenula (dHb), and that dHb SPX1 neurons project to the interpeduncular nucleus (IPN) (Kim et al, 2019)
Consistent with our previous observation that dHb SPX1 neurons project into the IPN, mCherry fluorescence was detected in the dHb, fasciculus retroflexus (FR), and IPN in this transgenic zebrafish (Figures 1C–F)
Summary
Spexin ( known as SPX, NPQ, and C12ORF39) is a secreted neuropeptide that is mainly expressed in the brain, pancreas, kidney, liver, ovary, and adrenal glands of mammals and fish (Mirabeau et al, 2007; Sonmez et al, 2009; Porzionato et al, 2010; Rucinski et al, 2010; Liu et al, 2013; Wong et al, 2013). The functional mature peptide domain of SPX consists of 14 amino acids (NWTPQAMLYLKGA/TQ), which have multiple physiological functions, including adrenocortical cell proliferation, cardiovascular function, urine flow, nociception, reproduction, and food intake (Rucinski et al, 2010; Toll et al, 2012; Liu et al, 2013; Wong et al, 2013; Ma et al, 2018).
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