Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK S7N 5E2, Canada.
Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK S7N 5E2, Canada.
Behav Brain Res. 2020 Apr 20;384:112514. doi: 10.1016/j.bbr.2020.112514. Epub 2020 Jan 28.
In recent years, there has been a growing appreciation that 17β-estradiol (E2) can rapidly modulate learning and memory processes by binding to membrane estrogen receptors and cause the activation of a number of signaling cascades within the central nervous system. In this study, we sought to investigate the effects of post-training administration of E2 (100 ng/g, 1 μg/g, 10 μg/g) and involvement of the estrogen receptors (ERs) using selective ER agonists on the consolidation of object recognition (OR) and object placement memory (OP) in adult male zebrafish. The general activation of ERs with the highest E2 dose improved consolidation of memory in both learning tasks within 1.45 h of administration. Activation of classical ERs (ERα and ERβ) improved consolidation of OR memory, but had no effect on fish performance in OP task. On the other hand, activation of G protein-coupled ER1 impaired and enhanced consolidation of OR and OP memories, respectively. Memory improvement in both tasks was accompanied by a marked up-regulation in the expression of genes encoding ionotropic and metabotropic glutamate receptors in a task-dependent manner. In contrast, the down-regulation in the expression of certain ionotropic glutamate receptors was observed in fish with impaired OR memory. Moreover, our study also revealed an increase in the transcript abundance of genes associated with synaptic protein synthesis (brain-derived neurotrophic factor, synaptophysin, and the mechanistic target of rapamycin). These results suggest that E2 may affect consolidation of memory in zebrafish likely through rapid changes in synaptic morphology and function.
近年来,人们越来越认识到,17β-雌二醇(E2)可以通过与膜雌激素受体结合,迅速调节学习和记忆过程,并在中枢神经系统内引起许多信号级联的激活。在这项研究中,我们试图探讨在成年雄性斑马鱼中,训练后给予 E2(100ng/g、1μg/g、10μg/g)以及使用选择性雌激素受体激动剂对雌激素受体(ERs)的参与对物体识别(OR)和物体位置记忆(OP)巩固的影响。最高剂量的 E2 可普遍激活 ERs,在给药后 1.45 小时内,可改善两种学习任务的记忆巩固。经典 ERs(ERα 和 ERβ)的激活改善了 OR 记忆的巩固,但对 OP 任务中的鱼类表现没有影响。另一方面,G 蛋白偶联受体 ER1 的激活分别损害和增强了 OR 和 OP 记忆的巩固。两种任务的记忆改善都伴随着与突触蛋白合成相关的基因(脑源性神经营养因子、突触小泡蛋白和雷帕霉素的作用靶点)的表达明显上调。相反,在 OR 记忆受损的鱼类中观察到某些离子型谷氨酸受体的表达下调。此外,我们的研究还揭示了与突触蛋白合成相关的基因(脑源性神经营养因子、突触小泡蛋白和雷帕霉素的作用靶点)转录丰度的增加。这些结果表明,E2 可能通过快速改变突触形态和功能来影响斑马鱼的记忆巩固。