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海馬區(qū)CRFR1受體介導間歇低氧誘導的新生鼠空間學習記憶增強

發(fā)布時間:2018-04-25 21:44

  本文選題:低氧 + 學習記憶 ; 參考:《浙江大學》2010年碩士論文


【摘要】:低氧(Hypoxia)是生物體在自然活動中可能受到的主要應激之一,它對包括人類在內的生物的發(fā)育、行為和健康狀況等有著重要影響。我們已經(jīng)報道了三或四周的適度間歇低氧(16% O2,4小時/天)可以促進新生小鼠的空間學習記憶,這種空間學習記憶能力的提高與CREB的磷酸化水平和海馬CA1區(qū)錐體細胞LTP的增強以及海馬樹突棘結構蛋白SPAR以及突觸后密度蛋白PSD95的上調等密切相關。 本研究通過實時定量PCR、Elisa、藥理學和行為學等方法,研究海馬CRF及其受體是否以及如何參與調節(jié)小鼠空間學習記憶能力的提高。我們的研究結果發(fā)現(xiàn)小鼠出生后經(jīng)歷間歇低氧導致發(fā)育期間生后P35海馬區(qū)CRF、CRFR1和IGFBP2表達上調;同時也發(fā)現(xiàn)間歇低氧可以促進海馬區(qū)IGFBP2的表達,IGFBP2和SPAR呈正相關,這種作用可以被IGFBP2抗體阻斷。此外,海馬原代神經(jīng)元培養(yǎng)研究顯示0.1nM CRF可以促進IGFBP2蛋白表達。上述發(fā)現(xiàn)意味著生后間歇低氧上調海馬區(qū)的CRF,通過CRFR1受體增加ⅠGFBP2的表達,從而促進樹突棘結構蛋白SPAR上調,增強新生小鼠的空間學習記憶能力。
[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,

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