模拟高原间歇性低氧对小鼠学习记忆功能的影响

发布时间：2018-03-08 03:36

本文选题：低氧　切入点：学习　出处：《浙江大学》2005年博士论文　论文类型：学位论文

【摘要】：低氧与人类密切相关。低氧改变生理功能,严重的低氧引起病理变化,但在某些情况下它对人体还有益处。神经系统,特别是大脑皮质对低氧最为敏感。人们更为关注的可能是低氧对认知功能的影响。记忆的研究近年来得到了飞速发展, 新的发现和成果不断出现,反映出人们越来越想知道人体最重要器官-大脑是如何工作的。根据不同的方式分类,记忆有不同的形式。本文在实验室条件下模拟海拔2千米(16.O%O_2;PaO2,60mmHg)和5千米(10.8%O_2;PaO2,41mmHg)高原低压低氧环境,观察了成年、出生后和胚胎期间歇性低氧(Intermittent hypoxia,IH) (4小时/天)暴露对小鼠空间和联合性学习记忆的影响。用Morris水迷宫和八臂迷宫测试空间学习记忆,穿梭箱用来测试联合性学习记忆。结果 1.与对照组(设为海平面,21%O_2)比较,出生后3周和4周2千米和5千米间歇性低氧显著地缩短了雄性小鼠(出生后36至40天,P36-40)在水迷宫中寻找站台的潜伏期,并增强了小鼠对原站台的记忆能力。其中2千米低氧小鼠的空间学习记忆增强能力可以一直持续到成年(P85-89)。出生后3周或4周2千米低氧也显著减少雄性和雌性小鼠(P60-68)在八臂迷宫中所犯错误次数。对于出生后 4周低氧小鼠在P36天进行研究发现:与对照组比较,电镜显示,4周2千米和5 千米低氧明显增加小鼠海马CA3区突触数目。电刺激Schaffer侧枝诱导5千米低氧小鼠CAl锥体细胞记录到幅度显著增大的LTP。western blot分析见低氧小鼠海马内磷酸化CREB(p-CREB)显著增加,免疫组织化学研究进一步揭示增加的 p-CREB主要在CA3区。免疫荧光研究发现,2千米和5千米低氧都诱导穿通纤维投射通路(CAl的放射层、腔隙层和分子层、CA3各部)和DG内侧轴突、门区的 PSA-NCAM表达和同源盒基因Pax6在嗅前核和盖带的表达增强。GFAP免疫阳性星形胶质细胞在2千米和5千米低氧小鼠海马各区都明显减少,RT-PCR分析发现诱导发育阶段神经干细胞向胶质细胞转化的FGF2 mRNA在海马的表达减弱。此外,4周2千米和5千米低氧也显著诱导纹状体内PSA-NCAM强表达。微透析技术对成年小鼠海马CA3区内氨基酸4小时低氧前、中、后实时监测可见,2千米和5千米低氧都促进海马内兴奋性谷氨酸和天冬氨酸的释放,而减少抑制性γ-氨基丁酸的浓度。
[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.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R188

【引证文献】