Neuropeptide Y deficiency induces anxiety-like behaviours in zebrafish (Danio rerio)

Abstract

Neuropeptide Y (NPY) controls energy homeostasis including orexigenic actions in mammalians and non-mammalians. Recently, NPY has attracted attention as a mediator of emotional behaviour and psychosomatic diseases. However, its functions are not fully understood. We established npy genedeficient (NPY-KO) zebrafish (Danio rerio) to assess the relationship between NPY and emotional behaviours. The NPY-KO zebrafish exhibited similar growth, but pomc and avp mRNA levels in the brain were higher as compared to wild-type fish. NPY-KO zebrafish exhibited several anxiety-like behaviours, such as a decrease in social interaction in mirror test and decreased locomotion in blackwhite test. The acute cold stress-treated NPY-KO zebrafish exhibited anxiety-like behaviours such as remaining stationary and swimming along the side of the tank in the mirror test. Moreover, expression levels of anxiety-associated genes (orx and cck) and catecholamine production (gr, mr, th1 and th2) were significantly higher in NPY-KO zebrafish than in wild-type fish. We demonstrated that NPY-KO zebrafish have an anxiety phenotype and a stress-vulnerability like NPY-KO mice, whereby orx and/or catecholamine signalling may be involved in the mechanism actions.

Neu1 deficiency induces abnormal emotional behavior in zebrafish

“…5 a). In general, adult zebrafish are known to instinctively prefer black to white areas because fish have a low risk of being detected by predators in a black background 23 . As expected, we noted that WT zebrafish stayed in the black area longer than in the white area during the 5 min analysis (Fig.…”

“…5 d), indicating that Neu1-KO zebrafish stayed on the white side for a longer time per invasion. In addition, zebrafish are known to feel anxious toward the white color 23 . As shown in Fig.…”

“…To examine the alteration of emotions in Neu1-KO zebrafish, we estimated the mRNA levels of anxiety-related genes in WT and Neu1-KO zebrafish brains. The mineralocorticoid receptor (Mr), which is also conserved in zebrafish 23 , is known to regulate the activity of the hypothalamic–pituitary–adrenal (HPA) axis during the stress response 29 . We found that the mr mRNA level was significantly downregulated in Neu1-KO zebrafish compared with that in WT (2.6-fold decrease, p < 0.05, Fig.…”

“…Fish are excellent experimental animals for the analysis of social interaction, including group formation, aggressiveness, social preference, and boldness. Most emotional related-genes are known to be conserved across vertebrates, and several methodologies of behavioral analysis have been established in fish 22 , 23 . In addition, recent studies have revealed that neu1 genes are conserved in fish species, with their enzymatic properties 24 – 27 .…”

Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction

“…Neuropeptide Y is a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function (https://www.ncbi.nlm.nih.gov/gene/4852). Neuropeptide Y deficiency is significantly linked to anxiety development in all animals including fish and human ( [94][95][96][97], see supplementary). The NPY expression is linked to only one PPAR-gamma; its positive effect on the NPY expression is known in arcuate hypothalamus [98].…”