Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
J Affect Disord. 2021 Mar 1;282:1195-1202. doi: 10.1016/j.jad.2020.12.190. Epub 2020 Dec 31.
The present study aims to evaluate the effects of ouabain on memory and neurotrophic parameters in the brains of rats.
Wistar rats received an intracerebroventricular (ICV) injection of ouabain or artificial cerebrospinal fluid (aCSF). Seven and 14 days after ICV administration, the animals were subjected to the open-field and splash tests. Furthermore, the pro-BDNF, BDNF, TrkB, and CREB were assessed in the frontal cortex and hippocampus of the rats, in both seven and 14 days after ICV injection. The memory of the animals was tested by novel object recognition test (NOR) and inhibitory avoidance task (IA), only 14 days after ICV administration.
Ouabain increased locomotion and exploration in the animals seven days after its administration; however, 14 days after ICV, these behavioral parameters return to the basal level. Seven days after ouabain administration increased grooming behavior in the splash test; on the other hand, seven days after ouabain injection decreased the grooming behavior, which is considered an anhedonic response. Besides, ouabain decreased recognition index in the NOR and decreased aversive memory in the IA, when compared to the control group. The levels of pro-BDNF and BDNF decreased in the frontal cortex seven days after ouabain; but its receptor (TrkB) and CREB decreased seven and 14 days after ouabain, in both cerebral structures evaluated.
Ouabain-induced animal model of BD is an excellent model to assess memory alteration, observed in bipolar patients. Besides, the memory impairment induced by ouabain seems to be related to BDNF signaling pathway alterations.
本研究旨在评估哇巴因对大鼠大脑中记忆和神经营养参数的影响。
Wistar 大鼠接受脑室（ICV）哇巴因或人工脑脊液（aCSF）注射。ICV 给药后 7 天和 14 天，动物进行旷场和飞溅测试。此外，在 ICV 给药后 7 天和 14 天评估大鼠前额皮质和海马中的 pro-BDNF、BDNF、TrkB 和 CREB。动物的记忆通过新物体识别测试（NOR）和抑制回避任务（IA）进行测试，仅在 ICV 给药后 14 天进行。
哇巴因给药后 7 天增加了动物的运动和探索；然而，14 天后，这些行为参数恢复到基础水平。哇巴因给药后 7 天增加了飞溅测试中的修饰行为；另一方面，哇巴因注射后 7 天减少了修饰行为，这被认为是一种快感缺失反应。此外，与对照组相比，NOR 中的识别指数降低，IA 中的回避记忆降低。与对照组相比，哇巴因给药后 7 天前额皮质中的 pro-BDNF 和 BDNF 水平降低；但在评估的两个脑结构中，其受体（TrkB）和 CREB 在 7 天和 14 天后均降低。
哇巴因诱导的 BD 动物模型是评估双相情感障碍患者记忆改变的理想模型。此外，哇巴因引起的记忆损伤似乎与 BDNF 信号通路改变有关。
