The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan.
Faculty of Fisheries, Kagoshima University, Kagoshima, Japan.
Sci Rep. 2021 Jun 29;11(1):13477. doi: 10.1038/s41598-021-92778-9.
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.
NEU1 唾液酸酶在溶酶体中水解糖缀合物上的唾液酸。NEU1 缺乏会导致唾液酸贮积症，其症状包括面部畸形、骨发育不良和神经退行性变。然而，NEU1 缺乏对情绪活动的影响尚未被探索。在这里，我们使用 Neu1 基因敲除斑马鱼（Neu1-KO）进行了行为分析。Neu1-KO 斑马鱼的游泳行为与野生型斑马鱼（WT）相似，但群体行为减少，鱼之间的距离比 WT 斑马鱼更大。攻击测试显示 Neu1-KO 斑马鱼的攻击行为比 WT 斑马鱼减少。在镜子和 3 室测试中，Neu1-KO 斑马鱼对镜子中的对手和多个陌生斑马鱼表现出更多的兴趣，而 WT 斑马鱼则不然。此外，Neu1-KO 斑马鱼还与不同种类的鱼表现出更多的互动，而 WT 斑马鱼则避开它们。在黑白偏好测试中，Neu1-KO 斑马鱼对白区表现出异常偏好，而 WT 斑马鱼则偏好黑区。Neu1-KO 斑马鱼的下丘脑-垂体-肾上腺轴相关基因下调，溶酶体出胞激活剂 lamp1a 上调，其大脑中积累了几种神经鞘糖脂。本研究表明，Neu1 缺乏导致斑马鱼出现异常的情绪行为，可能是由于溶酶体出胞引起的神经元功能障碍所致。
