Abstract
NEU1 sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes. Deficiency of NEU1 causes sialidosis with symptoms including facial dysmorphism, bone dysplasia, and neurodegeneration. However, the effects of NEU1 deficiency on emotional activity have not been explored. Here, we conducted the behavioral analysis using Neu1-knockout zebrafish (Neu1-KO). Neu1-KO zebrafish showed normal swimming similar to wild-type zebrafish (WT), whereas shoaling was decreased and accompanied by greater inter-fish distance than WT zebrafish. The aggression test showed a reduced aggressive behavior in Neu1-KO zebrafish than in WT zebrafish. In the mirror and 3-chambers test, Neu1-KO zebrafish showed more interest toward the opponent in the mirror and multiple unfamiliar zebrafish, respectively, than WT zebrafish. Furthermore, Neu1-KO zebrafish also showed increased interaction with different fish species, whereas WT zebrafish avoided them. In the black–white preference test, Neu1-KO zebrafish showed an abnormal preference for the white region, whereas WT zebrafish preferred the black region. Neu1-KO zebrafish were characterized by a downregulation of the anxiety-related genes of the hypothalamic–pituitary–adrenal axis and upregulation of lamp1a, an activator of lysosomal exocytosis, with their brains accumulating several sphingoglycolipids. This study revealed that Neu1 deficiency caused abnormal emotional behavior in zebrafish, possibly due to neuronal dysfunction induced by lysosomal exocytosis.
Highlights
neuraminidase 1 (NEU1) sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes
We found that Neu1-knockout zebrafish (Neu1-KO) zebrafish did not exhibit any abnormal behavior, such as freezing and limited swimming along the tank wall, and their swimming distance and average swimming speed did not differ from those of wild-type zebrafish (WT) (Fig. 1a–c)
We found that under acclimation conditions, the increased fish intervals were sustained in Neu1-KO zebrafish compared with those of WT zebrafish (p < 0.01, Fig. 1f)
Summary
NEU1 sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes. Deficiency of NEU1 causes sialidosis with symptoms including facial dysmorphism, bone dysplasia, and neurodegeneration. The aggression test showed a reduced aggressive behavior in Neu1-KO zebrafish than in WT zebrafish. Neu1-KO zebrafish were characterized by a downregulation of the anxiety-related genes of the hypothalamic–pituitary–adrenal axis and upregulation of lamp1a, an activator of lysosomal exocytosis, with their brains accumulating several sphingoglycolipids. This study revealed that Neu[1] deficiency caused abnormal emotional behavior in zebrafish, possibly due to neuronal dysfunction induced by lysosomal exocytosis. Several DNA mutations in the NEU1 gene in patients with sialidosis have been reported[2,11], with these mutations inducing alterations in the Scientific Reports | (2021) 11:13477. Activity of sialidase, lysosomal localization, complex formation, structure, and half-life of NEU1 polypeptides[12,13,14], leading to a significant impact on the symptoms of the disease
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