Thompson W Andrew, Shvartsburd Zachary, Vijayan Mathilakath M
Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
Aquat Toxicol. 2022 Jan;242:106041. doi: 10.1016/j.aquatox.2021.106041. Epub 2021 Nov 22.
Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a highly prescribed antidepressant and is detected at µg/L concentrations in waterways receiving municipal wastewater effluents. We previously showed that early-life venlafaxine exposure disrupted the normal development of the nervous system and reduces larval activity in zebrafish (Danio rerio). However, it is unclear whether the reduced swimming activity may be associated with impaired cardiac function. Here we tested the hypothesis that zygotic exposure to venlafaxine impacts the development and function of the larval zebrafish heart. Venlafaxine (0, 1 or 10 ng) was administered by microinjection into freshly fertilized zebrafish embryos (1-4 cell stage) to assess heart development and function during early-life stages. Venlafaxine deposition in the zygote led to precocious development of the embryo heart, including the timing of the first heartbeat, increased heart size, and a higher heart rate at 24- and 48-hours post-fertilization (hpf). Also, waterborne exposure to environmental levels of this antidepressant during early development increased the heart rate at 48 hpf of zebrafish larvae mimicking the zygotic deposition. The venlafaxine-induced higher heart rate in the embryos was abolished in the presence of NAN-190, an antagonist of the 5HT receptor. Also, heart rate dropped below control levels in the 10 ng, but not 1 ng venlafaxine group at 72 and 96 hpf. An acute stressor reduced the venlafaxine-induced heart rate at 48 hpf but did not affect the already reduced heart rate at 72 and 96 hpf in the 10 ng venlafaxine group. Our results suggest that the higher heart rate in the venlafaxine group may be due to an enhanced serotonin stimulation of the 5HT receptor. Taken together, early-life venlafaxine exposure disrupts cardiac development and has the potential to compromise the cardiovascular performance of larval zebrafish.
文拉法辛是一种选择性5-羟色胺和去甲肾上腺素再摄取抑制剂，是一种处方量很大的抗抑郁药，在接纳城市污水排放的水道中能检测到其浓度为微克/升。我们之前表明，生命早期接触文拉法辛会扰乱神经系统的正常发育，并降低斑马鱼（Danio rerio）幼体的活动能力。然而，尚不清楚游泳活动减少是否可能与心脏功能受损有关。在此，我们检验了一个假设，即合子期接触文拉法辛会影响斑马鱼幼体心脏的发育和功能。通过显微注射将文拉法辛（0、1或10纳克）注入刚受精的斑马鱼胚胎（1-4细胞期），以评估生命早期阶段心脏的发育和功能。合子中的文拉法辛沉积导致胚胎心脏早熟发育，包括首次心跳时间提前、心脏大小增加以及受精后24和48小时（hpf）时心率加快。此外，在早期发育期间环境水平的这种抗抑郁药的水体暴露增加了模拟合子沉积的斑马鱼幼体在48 hpf时的心率。在存在5HT受体拮抗剂NAN-190时文拉法辛诱导的胚胎心率升高被消除。而且，在72和96 hpf时10纳克文拉法辛组的心率降至对照水平以下，但1纳克文拉法辛组未出现这种情况。一种急性应激源降低了文拉法辛诱导的48 hpf时心率，但不影响10纳克文拉法辛组在72和96 hpf时已经降低的心率。我们的结果表明，文拉法辛组较高的心率可能是由于5HT受体的5-羟色胺刺激增强所致。综上所述，生命早期接触文拉法辛会扰乱心脏发育，并有可能损害斑马鱼幼体的心血管性能。
