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激肽 B1 和 B2 受体在小鼠衰老过程中记忆巩固中的作用。

Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

机构信息

Department of Physiological Sciences, Faculdade de Ciências Médicas da Santa Casa de São Paulo. Rua Dr. Cesario Motta Junior, 61, São Paulo, SP, CEP 01221-020, Brazil.

出版信息

Neuropeptides. 2010 Apr;44(2):163-8. doi: 10.1016/j.npep.2009.12.006. Epub 2010 Jan 8.

Abstract

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P<0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor.

摘要

在生理条件下,老年人会出现与神经元丢失相关的记忆缺陷。这种模式也与阿尔茨海默病有关,但在这种情况下,其程度更为严重。激肽受体参与神经退行性变和淀粉样β浓度的增加,与阿尔茨海默病(AD)有关。考虑到这些发现,本工作评估了激肽受体在衰老过程中记忆巩固中的作用。雄性 C57Bl/6(wt)、B1 敲除(koB1)或 B2 敲除(koB2)小鼠(3、6、12 和 18 个月龄 - mo;每组 10 只)接受主动回避装置中的获得性会话、学习强化(24 小时后:测试 1)和最终测试(7 天后:测试 2),以评估记忆。记录条件回避反应(CAR,50 次试验的%)。在获得性会话中,所有品系的同龄动物获得的 CAR 相似。然而,随着年龄的增长,CAR 明显下降(3mo:8.8+/-2.3%;6mo:4.1+/-0.6%;12mo:2.2+/-0.6%,18mo:3.6+/-0.6%,P<0.01),表明学习过程的减少。在测试 1 中,正如预期的那样,所有 3 个月和 6 个月龄的动物以及 12 个月龄的 wt 和 12 个月龄的 koB1 的记忆保留显著增加(P<0.05),与训练阶段相比。然而,12 个月龄的 koB2 和所有 18 个月龄的动物的记忆保留没有增加。在测试 2 中,所有年龄的 3 个月和 6 个月龄的 wt 和 koB1 小鼠的记忆均有显著改善(P<0.05),与测试 1 相比。然而,所有年龄的 12 个月龄的 wt 和 koB2 小鼠的记忆保留没有差异。我们认为,在衰老过程中,B1 受体可能参与神经退行性变和记忆丧失。然而,B2 受体显然起着神经保护因子的作用。

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