Moosavi Maryam, Abbasi Leila, Zarifkar Asadollah, Rastegar Karim
Shiraz Neuroscience Research Center and Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran; Nanotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Shiraz Neuroscience Research Center and Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmacol Biochem Behav. 2014 Jul;122:164-72. doi: 10.1016/j.pbb.2014.03.021. Epub 2014 Apr 2.
Nitric oxide (NO) is an important intercellular messenger in the control of physiologic functions. It is synthesized by 3 different nitric oxide synthase enzymes (NOS). Uses of non-selective NOS inhibitor (L-NAME) have shown that NO is involved in neuronal plasticity and memory. This study aimed to determine the differential role of NO in spatial memory formation steps. In addition, regarding the roles of ERK and CaMKII in hippocampal plasticity, the hippocampal ERK and CaMKII activities were assessed to identify the effect of L-NAME on those proteins during each phase of memory. Adult male Sprague-Dawely rats weighing 220-280 g were trained in a single session consisting of 8 trials. To evaluate the effect of L-NAME on acquisition, L-NAME (3 or 10 mg/kg/i.p.) was administered 30 min before training. To assess its effect on the consolidation phase, L-NAME (3 or 10 mg/kg/i.p.) was injected immediately after training and a probe test was carried out 24 h later to analyse memory retention. To determine its effect on memory retrieval L-NAME (3 or 10 mg/kg/i.p.) was injected 30 min before probe trial which was conducted 24 h after training. The hippocampi were isolated after behavioural studies and western blotting analysis on hippocampal lysates was performed to illustrate the levels of phosphorylated ERK and CaMKII. The results showed that pre-training administration of L-NAME in 10 mg/kg but not 3mg/kg deteriorates acquisition. Post-training and pre-probe administration of L-NAME in 10 mg/kg but not 3 mg/kg impaired animal's performance in probe test. Additionally L-NAME treatment decreased the amount of phosphorylated (activated) ERK and CaMKII in the hippocampus. This study showed that endogenous nitric oxide is involved not only in all stages of memory, but also in ERK and CaMKII activation in the hippocampus during all 3 stages of memory.
一氧化氮（NO）是控制生理功能的重要细胞间信使。它由3种不同的一氧化氮合酶（NOS）合成。使用非选择性NOS抑制剂（L-NAME）的研究表明，NO参与神经元可塑性和记忆。本研究旨在确定NO在空间记忆形成步骤中的不同作用。此外，鉴于ERK和CaMKII在海马可塑性中的作用，评估了海马ERK和CaMKII活性，以确定L-NAME在记忆各阶段对这些蛋白质的影响。体重220-280g的成年雄性Sprague-Dawely大鼠在由8次试验组成的单次训练中接受训练。为了评估L-NAME对记忆获取的影响，在训练前30分钟腹腔注射L-NAME（3或10mg/kg）。为了评估其对巩固阶段的影响，在训练后立即注射L-NAME（3或10mg/kg），并在24小时后进行探针试验以分析记忆保持情况。为了确定其对记忆检索的影响，在训练后24小时进行探针试验前30分钟注射L-NAME（3或10mg/kg）。行为学研究后分离海马，并对海马裂解物进行蛋白质印迹分析，以说明磷酸化ERK和CaMKII的水平。结果表明，10mg/kg而非3mg/kg的L-NAME训练前给药会损害记忆获取。10mg/kg而非3mg/kg的L-NAME训练后和探针试验前给药会损害动物在探针试验中的表现。此外，L-NAME处理降低了海马中磷酸化（活化）ERK和CaMKII的量。本研究表明，内源性一氧化氮不仅参与记忆的所有阶段，还参与记忆所有3个阶段中海马ERK和CaMKII的激活。
