Neuroscience Center, Helsinki Institute of Life Science HiLIFE, University of Helsinki, 00290, Helsinki, Finland.
Department of Anatomy, University of Helsinki, 00290, Helsinki, Finland.
Sci Rep. 2019 Feb 14;9(1):2036. doi: 10.1038/s41598-019-39347-3.
Neurotrophins and their receptors have highly conserved evolutionary lineage in vertebrates including zebrafish. The NTRK2 receptor has two isoforms in zebrafish, Ntrk2a and Ntrk2b. The spatio-temporal expression pattern of bdnf and ntrk2b in the zebrafish brain was studied using in situ hybridization. The robust and corresponding expression pattern of ntrk2b to bdnf suggests that ntrk2b is the key receptor for bdnf in the zebrafish brain, unlike its duplicate isoform ntrk2a. To study ntrk2b function, two different genetic strategies, the TILLING mutant and morpholino oligonucleotides (MO), were used. Specific subsets of the dopaminergic and serotonergic neuronal populations were affected in the mutants and morphants. The mutant showed anxiety- like behavior both in larval and adult stages. Our results consistently indicate that BDNF/NTRK2 signaling has a significant role in the development and maintenance of aminergic neuronal populations. Therefore, the ntrk2b-deficient zebrafish is well suited to study mechanisms relevant for psychiatric disorders attributed to a dysfunctional monoaminergic system.
神经生长因子及其受体在包括斑马鱼在内的脊椎动物中具有高度保守的进化谱系。NTRK2 受体在斑马鱼中有两种同工型，Ntrk2a 和 Ntrk2b。使用原位杂交技术研究了 bdnf 和 ntrk2b 在斑马鱼大脑中的时空表达模式。bdnf 和 ntrk2b 的表达模式非常相似，表明 ntrk2b 是斑马鱼大脑中 bdnf 的关键受体，而与其重复同工型 ntrk2a 不同。为了研究 ntrk2b 的功能，使用了两种不同的遗传策略，即 TILLING 突变体和 morpholino 寡核苷酸 (MO)。突变体和形态发生体中多巴胺能和 5-羟色胺能神经元群体的特定亚群受到影响。突变体在幼虫和成虫阶段都表现出类似焦虑的行为。我们的结果一致表明，BDNF/NTRK2 信号在胺能神经元群体的发育和维持中具有重要作用。因此，ntrk2b 缺陷型斑马鱼非常适合研究归因于单胺能系统功能障碍的精神疾病相关的机制。
