Effect of Rhizoma curcumae oil on the learning and memory in rats exposed to chronic hypoxia and the possible mechanisms / 生理学报

The effect of Rhizoma curcumae oil on the learning and memory in rats exposed to chronic hypoxia and the possible mechanisms were investigated. The rats were divided randomly into 5 groups (14 animals in each group): control, chronic hypoxia, chronic hypoxia with low (5 mg/kg body weight), middle (10 mg/kg body weight) and high (20 mg/kg body weight) concentrations of Rhizoma curcumae oil injection. The animals undergoing chronic hypoxia were exposed to hypoxia in a hypoxic chamber containing 10% O(2) and 5% CO(2) for 10 h/d, lasting 28 d. Morris water maze (MWM) test was used to obtain the scores of leaning and memory. The superoxide dismutase (SOD) activity and malonaldehyde (MDA) content were determined in the serum and hippocampus as well as [Ca(2+)](i) in the hippocampus. The expression of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CaMKII) in the hippocampus was evaluated by using immunohistochemistry and Western blot. Compared with the control group, the chronic hypoxia group showed the following changes: (1) The escape latency to the hidden platform was remarkably prolonged (P<0.05); (2) The content of MDA and [Ca(2+)](i) were obviously higher, but the activity of SOD and the expression of p-CaMKII were significantly lower (P<0.05, P<0.01). Compared with the chronic hypoxia group, groups with Rhizoma curcumae oil injection had the following changes: (1) The escape latency to the hidden platform was remarkably shorter in 10, 20 mg/kg body weight groups (P<0.05); (2) The content of MDA and [Ca(2+)](i) were markedly decreased in 5, 10, 20 mg/kg body weight groups (P<0.05, P<0.01), but the activity of SOD in the serum and the expression of p-CaMKII were significantly higher in 10, 20 mg/kg body weight groups (P<0.05, P<0.01). The results showed that the capacity of learning and memory was degraded following chronic hypoxia. The decrease in MDA content and [Ca(2+)](i) and (or) the increase in SOD activity and p-CaMKII expression might participate in the enhancing effect on learning and memory induced by Rhizoma curcumae oil.

Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the hippocampus of chronic multiple-stressed rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effect of chronic stress on cognitive functions has been one of the hot topic in neuroscience. But there has been much controversy over its mechanism. Such single stressor applied in the past could not simulate complicated living circumstances that people confronted with. The aim of this study was to investigate the effects of chronic multiple-stress on learning and memory as well as on the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), calmodulin (CaM) mRNA, and cAMP-response element binding protein (CREB) mRNA in the hippocampus of rats.</p><p><b>METHODS</b>The rats were divided randomly into stressed and control groups. The stressed group was given chronic multiple-stress for 6 weeks to set up a chronic multiple-stressed model. The rats' performance of spatial learning and memory was tested using Morris Water Maze (MWM) and Y-maze. Meanwhile, the expressions of CaMKII, CaM mRNA and CREB mRNA of rats' hippocampus were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the width of synaptic cleft and the thickness of post-synaptic densities (PSD) were observed in the hippocampal CA3 region of rats by electron microscopy.</p><p><b>RESULTS</b>After exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group (P < 0.05, P < 0.01). The width of synaptic cleft was smaller and the thickness of PSD was larger in the hippocampal CA3 region of the stressed group than in that of the control group (P < 0.01). The CaMK II immunostaining of the stressed group was stronger than that of the control group in the stratum radiatum and oriens of the hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis indicated that the expression of CaMK II, CaM mRNA, and CREB mRNA in the hippocampus of the stressed group was higher than that of the control group (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>The capacity of learning and memory can be enhanced after chronic multiple-stress. The increased levels of CaMK II, CaM mRNA, and CREB mRNA may contribute to the enhancing effect of chronic multiple-stress on learning and memory.</p>