海马区CRFR1受体介导间歇低氧诱导的新生鼠空间学习记忆增强

发布时间：2018-04-25 21:44

  本文选题：低氧 + 学习记忆　； 参考：《浙江大学》2010年硕士论文

【摘要】：低氧(Hypoxia)是生物体在自然活动中可能受到的主要应激之一,它对包括人类在内的生物的发育、行为和健康状况等有着重要影响。我们已经报道了三或四周的适度间歇低氧(16% O2,4小时/天)可以促进新生小鼠的空间学习记忆,这种空间学习记忆能力的提高与CREB的磷酸化水平和海马CA1区锥体细胞LTP的增强以及海马树突棘结构蛋白SPAR以及突触后密度蛋白PSD95的上调等密切相关。 本研究通过实时定量PCR、Elisa、药理学和行为学等方法,研究海马CRF及其受体是否以及如何参与调节小鼠空间学习记忆能力的提高。我们的研究结果发现小鼠出生后经历间歇低氧导致发育期间生后P35海马区CRF、CRFR1和IGFBP2表达上调；同时也发现间歇低氧可以促进海马区IGFBP2的表达,IGFBP2和SPAR呈正相关,这种作用可以被IGFBP2抗体阻断。此外,海马原代神经元培养研究显示0.1nM CRF可以促进IGFBP2蛋白表达。上述发现意味着生后间歇低氧上调海马区的CRF,通过CRFR1受体增加ⅠGFBP2的表达,从而促进树突棘结构蛋白SPAR上调,增强新生小鼠的空间学习记忆能力。
[Abstract]:Hypoxia (Hypoxia) is one of the major stresses that organisms may be subjected to in natural activities. It has an important effect on the development, behavior and health of organisms, including human beings. We have reported that three or four weeks of moderate intermittent hypoxia of 16% O2C4 / day can promote spatial learning and memory in newborn mice. The improvement of spatial learning and memory ability is closely related to the phosphorylation of CREB, the enhancement of LTP in the pyramidal cells of the hippocampal CA1 region, and the up-regulation of SPAR and PSD95, the hippocampal dendritic spinoprotein (SPAR) and postsynaptic density protein (PSD95). In this study, we studied whether and how hippocampal CRF and its receptors were involved in regulating spatial learning and memory ability of mice by real-time quantitative PCR Elisa, pharmacology and behavior. Our results showed that postnatal intermittent hypoxia induced the up-regulation of CRFFFR1 and IGFBP2 in postnatal P35 hippocampal area, and that intermittent hypoxia could promote the expression of IGFBP2 in hippocampus. There was a positive correlation between IGFBP2 and SPAR. This effect can be blocked by IGFBP2 antibodies. In addition, hippocampal primary neuron culture studies showed that 0.1nM CRF could promote the expression of IGFBP2 protein. These findings suggest that intermittent hypoxia after birth upregulated CRF in hippocampus and increased the expression of 鈪，

本文编号：1803104