Department of Pharmacology and Therapeutics, Health Science Center, State University of Maringá, Maringá, Paraná 87020-900, Brazil.
Department of Pharmacology and Therapeutics, Health Science Center, State University of Maringá, Maringá, Paraná 87020-900, Brazil..
Physiol Behav. 2017 Aug 1;177:196-207. doi: 10.1016/j.physbeh.2017.05.009. Epub 2017 May 5.
A series of our previous studies demonstrated that fish oil (FO), equivalent to 300mg/kg docosahexahenoic acid (DHA), facilitates memory recovery after transient, global cerebral ischemia (TGCI) in the aversive radial maze (AvRM). The present study sought to address two main issues: (i) whether the memory-protective effect of FO that has been observed in the AvRM can be replicated in the passive avoidance test (PAT) and object location test (OLT) and (ii) whether FO at doses that are lower than those used previously can also prevent TGCI-induced memory loss. In Experiment 1, naive rats were trained in the PAT, subjected to TGCI (4-vessel occlusion model), and tested for retrograde memory performance 8 and 15days after ischemia. Fish oil (300mg/kg/day DHA) was given orally for 8days. The first dose was delivered 4h postischemia. In Experiment 2, the rats were subjected to TGCI, treated with the same FO regimen, and then trained and tested in the OLT. In Experiment 3, the rats were trained in the AvRM, subjected to TGCI, administered FO (100, 200, and 300mg/kg DHA), and tested for memory performance up to 3weeks after TGCI. At the end of the behavioral tests, the brains were examined for neurodegeneration and neuroblast proliferation. All of the behavioral tests (PAT, OLT, and AvRM) were sensitive to ischemia, but only the AvRM was able to detect the memory-protective effect of FO. Ischemia-induced neurodegeneration and neuroblast proliferation were unaffected by FO treatment. These results suggest that (i) the beneficial effect of FO on memory recovery after TGCI is task-dependent, (ii) doses of FO<300mg/kg DHA can protect memory function in the radial maze, and (iii) cognitive recovery occurs in the absence of neuronal rescue and/or hippocampal neurogenesis.
我们之前的一系列研究表明，鱼油（FO），相当于 300mg/kg 二十二碳六烯酸（DHA），有助于在厌恶性放射臂迷宫（AvRM）中恢复短暂全脑缺血（TGCI）后的记忆。本研究旨在解决两个主要问题：（i）FO 在 AvRM 中观察到的记忆保护作用是否可以在被动回避测试（PAT）和物体位置测试（OLT）中复制，以及（ii）FO 剂量是否低于以前使用的剂量也可以预防 TGCI 引起的记忆丧失。在实验 1 中，未接受过训练的大鼠在 PAT 中接受训练，然后进行 TGCI（四血管闭塞模型），并在缺血后 8 天和 15 天进行逆行记忆表现测试。鱼油（300mg/kg/天 DHA）经口给予 8 天。第一次剂量在缺血后 4 小时给予。在实验 2 中，大鼠接受 TGCI 治疗，给予相同的 FO 方案，然后在 OLT 中接受训练和测试。在实验 3 中，大鼠在 AvRM 中接受训练，接受 TGCI，给予 FO（100、200 和 300mg/kg DHA），并在 TGCI 后 3 周内进行记忆表现测试。在行为测试结束时，检查大脑的神经退行性变和神经母细胞增殖。所有行为测试（PAT、OLT 和 AvRM）均对缺血敏感，但只有 AvRM 能够检测到 FO 的记忆保护作用。FO 处理对缺血引起的神经退行性变和神经母细胞增殖没有影响。这些结果表明：（i）FO 对 TGCI 后记忆恢复的有益作用取决于任务，（ii）FO 剂量<300mg/kg DHA 可保护放射臂迷宫中的记忆功能，以及（iii）认知恢复发生在没有神经元挽救和/或海马神经发生的情况下。
