CAJ | 학술논문

条件性presenilins双基因敲除小鼠(dKO小鼠)表现出类似阿尔茨海默症(AD)的大部分神经退行性病症,如Tau蛋白磷酸化、神经元凋亡、皮层萎缩以及认知能力受损等.为探讨presenilins功能缺失、神经退行性症状与单胺类递质变化的相关性,利用毛细管电泳法检测6、9和12月龄dKO小鼠皮层、海马及其他前脑部位中各单胺类神经递质的含量.结果显示,与对照组相比,dKO小鼠皮层中单胺类神经递质在6月龄时显著降低,而随着年龄的增长,神经退行性病变加剧,递质浓度也均明显上升,在海马区,dKO小鼠单胺类递质则呈上升趋势,但仅6月龄时5-羟色胺和肾上腺素及12月龄时各递质的上升有统计学意义,前脑其他部位5-羟色胺和多巴胺递质在6、9月龄时与对照组相近,在12月龄时则显著降低,而去甲肾上腺素和肾上腺素在6月和12月龄时均呈降低趋势,且均有统计学差异(6月龄肾上腺素除外).实验表明,单胺类神经递质在presenilins双基因敲除的小鼠前脑各区域中的水平均发生了随龄化的变化,且在前脑皮层、海马与前脑其他区域的变化趋势各有不同,而单胺类递质的变化是presenilins双基因敲除导致的直接结果还是间接结果,单胺类递质在AD样神经退性行病变中的作用如何,还有待于进一步的研究.
조건성presenilins쌍기인고제소서(dKO소서)표현출유사아이자해묵증(AD)적대부분신경퇴행성병증,여Tau단백린산화、신경원조망、피층위축이급인지능력수손등.위탐토presenilins공능결실、신경퇴행성증상여단알류체질변화적상관성,이용모세관전영법검측6、9화12월령dKO소서피층、해마급기타전뇌부위중각단알류신경체질적함량.결과현시,여대조조상비,dKO소서피층중단알류신경체질재6월령시현저강저,이수착년령적증장,신경퇴행성병변가극,체질농도야균명현상승,재해마구,dKO소서단알류체질칙정상승추세,단부6월령시5-간색알화신상선소급12월령시각체질적상승유통계학의의,전뇌기타부위5-간색알화다파알체질재6、9월령시여대조조상근,재12월령시칙현저강저,이거갑신상선소화신상선소재6월화12월령시균정강저추세,차균유통계학차이(6월령신상선소제외).실험표명,단알류신경체질재presenilins쌍기인고제적소서전뇌각구역중적수평균발생료수령화적변화,차재전뇌피층、해마여전뇌기타구역적변화추세각유불동,이단알류체질적변화시presenilins쌍기인고제도치적직접결과환시간접결과,단알류체질재AD양신경퇴성행병변중적작용여하,환유대우진일보적연구.
Conditional forebrain-specific presenilin-1 and presenilin-2 double knockout mice (dKO mice) exhibit several neurodegenerative phenotypes of Alzheimer's disease (AD) pathology, such as tau hyperphosphorylation, neuron loss, forebrain cortical shrinkage and memory impairment. By using capillary electrophoresis assay, monoamine neurotransmitters in forebrain cortex, hippocampus and other forebrain region of dKO mice aged at 6, 9 and 12 months were measured to illustrate the relationship among presenilins function deficiency, neurodegenerative phenotypes and monoamine neurotransmitters. Data showed that levels of monoamine neurotransmitters in forebrain cortex of dKO mice were significantly decreased at 6 months when compared to controls, while as mice getting older, levels of monoamine neurotransmitters increased to that of controls, or even higher. In hippocampus, 5-hydroxytryptamin and epinephrine in dKO mice had a significant increase at 6 months, followed with a significant increase of each monoamine neurotransmitter at 12 months age. In other forebrain region, 5-hydroxytryptamin and dopamine had a similar level between control and dKO mice at 6 and 9 months but a significant decrease at 12 months; however, level of norepinephrine and epinephrine were significantly decreased at 6 and 12 months except epinephrine of 6 months. These results demonstrated that knockout of presenilins genes could lead to the variation of monoamine neurotransmitters, and the variation profiles were different among forebrain cortex, hippocampus and other forebrain region. However, whether presenilins deficiency caused the variation of monoamine neurotransmitter directly or not, and how about the effects of variation of monoamine neurotransmitters on AD-like pathology need to be further analyzed.