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模擬高原間歇性低氧對(duì)小鼠學(xué)習(xí)記憶功能的影響

發(fā)布時(shí)間:2018-03-08 03:36

  本文選題:低氧 切入點(diǎn):學(xué)習(xí) 出處:《浙江大學(xué)》2005年博士論文 論文類(lèi)型:學(xué)位論文


【摘要】:低氧與人類(lèi)密切相關(guān)。低氧改變生理功能,嚴(yán)重的低氧引起病理變化,但在 某些情況下它對(duì)人體還有益處。神經(jīng)系統(tǒng),特別是大腦皮質(zhì)對(duì)低氧最為敏感。人 們更為關(guān)注的可能是低氧對(duì)認(rèn)知功能的影響。記憶的研究近年來(lái)得到了飛速發(fā)展, 新的發(fā)現(xiàn)和成果不斷出現(xiàn),反映出人們?cè)絹?lái)越想知道人體最重要器官-大腦是如何 工作的。根據(jù)不同的方式分類(lèi),記憶有不同的形式。本文在實(shí)驗(yàn)室條件下模擬海 拔2千米(16.O%O_2;PaO2,60mmHg)和5千米(10.8%O_2;PaO2,41mmHg)高原低 壓低氧環(huán)境,觀察了成年、出生后和胚胎期間歇性低氧(Intermittent hypoxia,IH) (4小時(shí)/天)暴露對(duì)小鼠空間和聯(lián)合性學(xué)習(xí)記憶的影響。用Morris水迷宮和八臂迷 宮測(cè)試空間學(xué)習(xí)記憶,穿梭箱用來(lái)測(cè)試聯(lián)合性學(xué)習(xí)記憶。 結(jié)果 1.與對(duì)照組(設(shè)為海平面,21%O_2)比較,出生后3周和4周2千米和5千 米間歇性低氧顯著地縮短了雄性小鼠(出生后36至40天,P36-40)在水迷宮中尋 找站臺(tái)的潛伏期,并增強(qiáng)了小鼠對(duì)原站臺(tái)的記憶能力。其中2千米低氧小鼠的空 間學(xué)習(xí)記憶增強(qiáng)能力可以一直持續(xù)到成年(P85-89)。出生后3周或4周2千米低 氧也顯著減少雄性和雌性小鼠(P60-68)在八臂迷宮中所犯錯(cuò)誤次數(shù)。對(duì)于出生后 4周低氧小鼠在P36天進(jìn)行研究發(fā)現(xiàn):與對(duì)照組比較,電鏡顯示,4周2千米和5 千米低氧明顯增加小鼠海馬CA3區(qū)突觸數(shù)目。電刺激Schaffer側(cè)枝誘導(dǎo)5千米低 氧小鼠CAl錐體細(xì)胞記錄到幅度顯著增大的LTP。western blot分析見(jiàn)低氧小鼠海 馬內(nèi)磷酸化CREB(p-CREB)顯著增加,免疫組織化學(xué)研究進(jìn)一步揭示增加的 p-CREB主要在CA3區(qū)。免疫熒光研究發(fā)現(xiàn),2千米和5千米低氧都誘導(dǎo)穿通纖維 投射通路(CAl的放射層、腔隙層和分子層、CA3各部)和DG內(nèi)側(cè)軸突、門(mén)區(qū)的 PSA-NCAM表達(dá)和同源盒基因Pax6在嗅前核和蓋帶的表達(dá)增強(qiáng)。GFAP免疫陽(yáng)性 星形膠質(zhì)細(xì)胞在2千米和5千米低氧小鼠海馬各區(qū)都明顯減少,RT-PCR分析發(fā)現(xiàn) 誘導(dǎo)發(fā)育階段神經(jīng)干細(xì)胞向膠質(zhì)細(xì)胞轉(zhuǎn)化的FGF2 mRNA在海馬的表達(dá)減弱。此 外,4周2千米和5千米低氧也顯著誘導(dǎo)紋狀體內(nèi)PSA-NCAM強(qiáng)表達(dá)。微透析技 術(shù)對(duì)成年小鼠海馬CA3區(qū)內(nèi)氨基酸4小時(shí)低氧前、中、后實(shí)時(shí)監(jiān)測(cè)可見(jiàn),2千米 和5千米低氧都促進(jìn)海馬內(nèi)興奮性谷氨酸和天冬氨酸的釋放,而減少抑制性γ-氨 基丁酸的濃度。
[Abstract]:Hypoxia is closely related to human beings. Hypoxic changes the physiological function, and the severe hypoxia causes pathological changes, but it is not possible.
In some cases it is beneficial to the human body. The nervous system, especially the cerebral cortex, is most sensitive to hypoxia.
More attention is given to the effect of hypoxia on cognitive function. The study of memory has developed rapidly in recent years.
New discoveries and results are emerging, reflecting the growing desire to know the most important organ of the human body - how the brain is
Work. According to different ways, memory has different forms. This paper simulates the sea under laboratory conditions.
2 kilometre (16.O%O_2; PaO2,60mmHg) and 5 km (10.8%O_2; PaO2,41mmHg) Gao Yuandi
In the hypoxic environment, the Intermittent hypoxia (IH) of adult, postnatal and embryonic period of intermittent hypoxia (IH) was observed.
Effects of exposure (4 hours / day) on space and association learning and memory in mice. Using the Morris water maze and eight arm fans
The palace tests space learning and memory, and the shuttle box is used to test joint learning and memory.
Result
1. compared with the control group (set for sea level, 21%O_2), 3 and 4 weeks after birth of 2 km and 5 thousand
Intermittent hypoxia significantly shortened the male mice (36 to 40 days after birth, P36-40) in the water maze.
The incubation period of the platform was found, and the memory ability of the mice to the original platform was enhanced. The empty 2 kilometer hypoxia mice
The ability to enhance learning and memory can continue to reach adulthood (P85-89). 3 or 4 weeks after birth, 2 kilometre is low
Oxygen also significantly reduced the number of errors in the male and female mice (P60-68) in the eight arm maze.
4 weeks of hypoxia mice in P36 days found that: compared with the control group, the electron microscope showed that 2 km and 5 weeks were 4 weeks.
Kilometer hypoxia significantly increased the number of synapses in the CA3 region of the hippocampus of mice. Electrical stimulation of Schaffer lateral branches was induced by 5 km low
The LTP.western blot analysis of CAl pyramidal cells in oxygen mice was significantly increased in the hypoxic mice sea
Manoi phosphorylation of CREB (p-CREB) increased significantly, immunohistochemical study revealed further increased
P-CREB is mainly in the CA3 region. Immunofluorescence studies have found that 2 and 5 km of hypoxia induce perforating fibers
The projective pathway (the radiological layer of the CAl, the lacunar and molecular layers, the CA3 parts) and the DG medial axons, the portal area
The expression of PSA-NCAM and homeobox gene Pax6 in the anterior olfactory nucleus and cover with enhanced expression of.GFAP immunoreactive
Astrocytes were significantly reduced in the hippocampus of 2 km and 5 km hypoxia mice. RT-PCR analysis found that astrocytes were significantly reduced.
The expression of FGF2 mRNA in the hippocampus weakened by the induction of neural stem cells to glial cells at the stage of development.
In addition, 4 weeks of 2 and 5 kilometer hypoxia also significantly induced strong expression of PSA-NCAM in the striate. Microdialysis technique
The amino acids in the hippocampal CA3 area of adult mice were observed before 4 HH hypoxia, and 2 km were observed in real time.
And 5 kilometer hypoxia both promote the release of excitatory glutamic acid and aspartic acid in the hippocampus, and reduce the inhibitory gamma ammonia
The concentration of butyric acid.

【學(xué)位授予單位】:浙江大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2005
【分類(lèi)號(hào)】:R188

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 丁學(xué)鵬;間歇性低氧對(duì)新生小鼠空間學(xué)習(xí)記憶的影響[D];浙江大學(xué);2006年

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本文編號(hào):1582262

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