端粒酶基因敲除小鼠行为学特征的增龄性变化研究
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摘要
目的通过对端粒酶基因敲除小鼠衰老特点的初步认识,为衰老领域的相关研究提供实验依据。方法分别选用2、3、5、7和9月龄的纯合子与同月龄的野生型端粒酶基因敲除小鼠相对照,从老化度评分、Morris水迷宫实验和自主活动实验等方面观察纯合子小鼠行为活动的增龄性变化。结果与野生型小鼠比较,纯合子小鼠随月龄增加其老化度评分呈升高趋势,且5、7和9月龄的老化度评分高于同龄野生型小鼠(P<0.05);Morris水迷宫实验中,相比较野生型小鼠,纯合子小鼠定位航行试验的逃避潜伏期随月龄增加而有增长趋势,且7和9月龄的逃避潜伏期长于同龄野生型小鼠(P<0.05),而在空间探索试验的逃避潜伏期目标象限时间随月龄增加而呈下降趋势,与野生型小鼠比较差异有统计学意义(P<0.05);自主活动实验结果显示,2、3和5月龄纯合子小鼠固定时间内自主活动次数与同龄野生型小鼠比较无显著变化,而7和9月龄纯合子小鼠与同龄野生型小鼠比较固定时间内自主活动次数减少(P<0.05)。结论与同龄野生型端粒酶基因敲除小鼠比较,纯合子端粒酶基因敲除小鼠随月龄增大,其行为活动出现明显增龄性变化,表现出系列衰老特征,尤其7和9月龄衰老表现更为明显。
Objective To systematically study aging changes of behavior characteristics in the telomerase knockout mice, so as to provide experimental basis for research in the field of aging using the model mice.Methods Homozygote telomerase knockout mice of 2, 3, 5, 7 and 9 months were selected and compared with wild telomerase knockout mice of the corresponding age. The aging changes of behavior characteristics in the homozygote mice were observed from aging degree score, Morris water maze experiment and independent activity experiment. Results Compared with the wild type mice, the homozygote mice showed an increasing trend of aging degree score, which was specially obvious in the mice of 5, 7 and 9 months compared with the wild type mice of the corresponding age(P < 0.05). In the Morris water maze experiment, compared with the wild type mice, the homozygote mice had a growing trend in sea trial with the increase of months, the escape latency of the 7- and 9-month homozygote mice was significantly longer than that of the wild type mice of the corresponding age(P < 0.05); while in the space exploration trial the escape latency of the target quadrant showed a downward trend with increasing month age, which was statistically different from that of the wild mice(P < 0.05). The independent activity experiment revealed, there were no significant changes in the number of autonomic activities within a fixed time between the homozygote mice and the wild type mice of 2, 3 and 5 months, while the number of autonomic activities within a fixed time in the homozygote mice of 7 and 9 months was significantly reduced compared to the wild mice of the corresponding age(P < 0.05).Conclusions Compared with wild type telomerase knockout mice of the same age, the homozygote mice have apparent aging changes in their activities, and show a series of aging characteristics, particularly in mice of 7and 9 months.
Objective To systematically study aging changes of behavior characteristics in the telomerase knockout mice, so as to provide experimental basis for research in the field of aging using the model mice.Methods Homozygote telomerase knockout mice of 2, 3, 5, 7 and 9 months were selected and compared with wild telomerase knockout mice of the corresponding age. The aging changes of behavior characteristics in the homozygote mice were observed from aging degree score, Morris water maze experiment and independent activity experiment. Results Compared with the wild type mice, the homozygote mice showed an increasing trend of aging degree score, which was specially obvious in the mice of 5, 7 and 9 months compared with the wild type mice of the corresponding age(P < 0.05). In the Morris water maze experiment, compared with the wild type mice, the homozygote mice had a growing trend in sea trial with the increase of months, the escape latency of the 7- and 9-month homozygote mice was significantly longer than that of the wild type mice of the corresponding age(P < 0.05); while in the space exploration trial the escape latency of the target quadrant showed a downward trend with increasing month age, which was statistically different from that of the wild mice(P < 0.05). The independent activity experiment revealed, there were no significant changes in the number of autonomic activities within a fixed time between the homozygote mice and the wild type mice of 2, 3 and 5 months, while the number of autonomic activities within a fixed time in the homozygote mice of 7 and 9 months was significantly reduced compared to the wild mice of the corresponding age(P < 0.05).Conclusions Compared with wild type telomerase knockout mice of the same age, the homozygote mice have apparent aging changes in their activities, and show a series of aging characteristics, particularly in mice of 7and 9 months.
引文
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[2]SAMPER E,FERNANDEZ P,EGUIA R,et al.Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells[J].Blood,2002,99(8):2767-2775.
[3]HOSOKAWA M,KASAI R,HIGUCHI K,et al.Grading score system:a method for evaluation of the degree of senescence in senescence accelerated mouse(SAM)[J].Mech Ageing Dev,1984,26(1):91-102.
[4]BLASCO M A,LEE H W,HANDE M P,et al.Telomere shortening and tumor formation by mouse cells lacking telomerase RNA[J].Cell,1997,91(1):25-34.
[5]PANOSSIAN L A,PORTER V R,VALENZUELA H F,et al.Telomere shortening in T cells correlates with Alzheimer's disease status[J].Neurobiol Aging,2003,24(1):77-84.
[6]ZHANG J,KONG Q,ZHANG Z,et al.Telomere dysfunction of lymphocytes in patients with Alzheimer disease[J].Cogn Behav Neurol,2003,16(3):170-176.
[7]MAEDA T,GUAN J Z,KOYANAGI M,et al.Aging-associated alteration of telomere length and subtelomeric status in female patients with Parkinson's disease[J].J Neurogenet,2012,26(2):245-251.
[8]KOLIADA A K,VA魲SERMAN A M,KRASNENKOV D S,et al.The study of telomere length in patients with Parkinson's disease[J].Zh Nevrol Psikhiatr Im S S Korsakova,2014,114(8):58-61.
[9]ZHAN Y,SONG C,KARLSSON R,et al.Telomere length shortening and alzheimer disease-a mendelian randomization study[J].JAMA Neurol,2015,72(10):1202-1203.
[10]MORRIS R.Developments of a water-maze procedure for studying spatial learning in the rat[J].J Neurosci Methods,1984,11(1):47-60.
[11]涂人顺,张国玺,孙斌辉.关于小鼠自主活动规律的研究[J].中国药理学通报,2002,4:464-465.