Dataset Information

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

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.

SUBMITTER: Jeong I

PROVIDER: S-EPMC6702259 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Jeong Inyoung I Kim Eunmi E Seong Jae Young JY Park Hae-Chul HC

Frontiers in neural circuits 20190814

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 ...[more]

PMID: 31474838

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Project description:Simple Summary Enhanced feeding can be associated with aggressive behaviour since food resources are the main reason for agonistic behaviour (any social behaviour related to fighting). The overexpression of the gene agouti-signalling protein (Asip1) in transgenic zebrafish (asip1-Tg) results in enhanced food intake and linear growth. Our next question was if asip1-Tg animals exhibit a dominant phenotype associated with the feeding-enhanced levels when compared to wild-type (WT) fish. To address this question, we quantified the aggressive behaviour by conducting dyadic fights with real opponents as well as by exposing the animals to their specular image using mirrors. The results indicate that asip1-Tg are less aggressive than WT zebrafish in both dyadic fights and mirror-stimulus tests. These findings provide direct evidence of the role of the melanocortin system in the regulation of fish behaviour. The subordinate personality observed in asip1-Tg suggests that this transgene would be non-threatening to native populations in the event of an escape from aquaculture facilities. These results provide a genetic modification strategy to enhance growth in fish through high feeding motivation without promoting aggressiveness. This suggests that inhibiting the melanocortin system could be a viable target for genetically engineered fish. It is worth noting that the regulatory approval for such genetically engineered fish would be subject to the guidelines and regulations of the U.S. Food and Drug Association. Abstract Feeding motivation plays a crucial role in food intake and growth. It closely depends on hunger and satiation, which are controlled by the melanocortin system. Overexpression of the inverse agonist agouti-signalling protein (ASIP) and agouti-related protein (AGRP) leads to enhanced food intake, linear growth, and weight. In zebrafish, overexpression of Agrp leads to the development of obesity, in contrast to the phenotype observed in transgenic zebrafish that overexpress asip1 under the control of a constitutive promoter (asip1-Tg). Previous studies have demonstrated that asip1-Tg zebrafish exhibit larger sizes but do not become obese. These fish display increased feeding motivation, resulting in a higher feeding rate, yet a higher food ration is not essential in order to grow larger than wild-type (WT) fish. This is most likely attributed to their improved intestinal permeability to amino acids and enhanced locomotor activity. A relationship between high feeding motivation and aggression has been previously reported in some other transgenic species showing enhanced growth. This study aims to elucidate whether the hunger observed in asip1-Tg is linked to aggressive behaviour. Dominance and aggressiveness were quantified using dyadic fights and mirror-stimulus tests, in addition to the analysis of basal cortisol levels. The results indicate that asip1-Tg are less aggressive than WT zebrafish in both dyadic fights and mirror-stimulus tests.

Dataset Information

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

Publications

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

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