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雄性大鼠寿命的纹状体多巴胺依赖性。用(-)司来吉兰进行的寿命研究。

The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl.

作者信息

Knoll J

机构信息

Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.

出版信息

Mech Ageing Dev. 1988 Dec;46(1-3):237-62. doi: 10.1016/0047-6374(88)90128-5.

Abstract

Long-term experiments on male rats revealed that better performers in the mating test are better learners in the shuttle box and the more active animals live significantly longer than their less active peers. It was established by the aid of (-)deprenyl, a highly specific chemical tool, which increases superoxide dismutase activity in the striatum, facilitates the activity of the nigrostriatal dopaminergic neurons with utmost selectivity, and protects these neurons from their age-related decay, that the efficiency of a male rat in behavioral tests, as well as the duration of its life are striatal dopamine dependent functions. As a measure of striatal function, sexual activity was tested once a week in a group of male rats (n = 132) from the 24th month of their life. Because of the age-related decay of this function none of the 2-year-old animals displayed full scale sexual activity. By dividing the group equally the rats were treated with saline (1 ml/kg, s.c.) and deprenyl (0.25 mg/kg, s.c.), respectively, three times a week. In the saline-treated group (n = 66) the last signs of sexual activity vanished to the 33rd week of treatment. (-)Deprenyl treatment restored full scale sexual activity in 64 out of 66 rats. The longest living rat in the saline-treated group lived 164 weeks. The average lifespan of the group was 147.05 +/- 0.56 weeks. The shortest living animal in the (-)deprenyl-treated group lived 171 weeks and the longest living rat died during the 226th week of its life. The average lifespan was 197.98 +/- 2.36 weeks, i.e. higher than the estimated maximum age of death in the rat (182 weeks). This is the first instance that by the aid of a well-aimed medication members of a species lived beyond the known lifespan maximum.

摘要

对雄性大鼠的长期实验表明,在交配测试中表现较好的大鼠在穿梭箱实验中也是更好的学习者,而且更活跃的动物比不太活跃的同类活得明显更长。借助(-)司来吉兰(一种高度特异性的化学工具)证实,雄性大鼠在行为测试中的效率以及其寿命长短均为纹状体多巴胺依赖性功能。(-)司来吉兰可增加纹状体中超氧化物歧化酶的活性,极其选择性地促进黑质纹状体多巴胺能神经元的活性,并保护这些神经元免于与年龄相关的衰退。作为纹状体功能的一项指标,从一组雄性大鼠(n = 132)24月龄起,每周对其性活动进行一次测试。由于该功能会随着年龄增长而衰退,2岁的动物均未表现出全面的性活动。将该组大鼠平均分成两组,分别每周皮下注射三次生理盐水(1 ml/kg)和司来吉兰(0.25 mg/kg)。在生理盐水处理组(n = 66)中,性活动的最后迹象在治疗第33周消失。(-)司来吉兰治疗使66只大鼠中的64只恢复了全面的性活动。生理盐水处理组中寿命最长的大鼠活了164周。该组的平均寿命为147.05±0.56周。(-)司来吉兰治疗组中寿命最短的动物活了171周,寿命最长的大鼠在其生命的第226周死亡。平均寿命为197.98±2.36周,即高于大鼠已知的最大死亡年龄(182周)。这是首次通过精准用药使一个物种的成员活到超过已知的最大寿命。

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