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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Sparing by rasagiline (TVP-1012) of cholinergic functions and behavior in the postnatal anoxia rat.
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Sparing by rasagiline (TVP-1012) of cholinergic functions and behavior in the postnatal anoxia rat.

机译：雷沙吉兰（TVP-1012）对产后缺氧大鼠胆碱能功能和行为的保护。

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Rasagiline (N-propargyl-1(R)aminoindan) is a selective and potent MAO-B inhibitor currently under development as the mesylate salt (TVP-1012) for the treatment of various neurologic disorders. Preliminary work in adult and senescent rats, either normal or hypoxia-lesioned, showed that chronic rasagiline treatment improved performance in memory and learning tasks, suggesting some beneficial effect on central cholinergic function. We have now used the postnatal anoxia-lesioned rat as a model of cholinergic dysfunction. In the neonatal rat, anoxia strongly affects the cholinergic system, which has not yet reached full maturation at this state of life. Rasagiline mesylate was administered from day 1 to completion of the study (day 60), first through nursing mother milk until weaning (day 21), then in drinking water, at the rate of 0.5 mg/kg/day. Drug access to the CNS was verified by analysis of MAO activity in brain (at 21 days). Treatment improved the juvenile hyperactivity syndrome associated with anoxia (at day 28). It improved performance in the passive avoidance test to normal control level (at day 40). It improved spatial memory performance in the Morris water maze to normal control level (at day 50). The untreated anoxia group failed in these tasks and was significantly inferior to either the normal control and rasagiline-treated anoxia groups. Determination of ChAT activity in the caudate and hippocampus of rats from each of these groups gave the following results (pmol ACh/mg protein/min). Caudate: normal control, 588 +/- 56; anoxia, 398 +/- 54; rasagiline-treated anoxia, 536 +/- 35. Hippocampus: normal control, 380 +/- 31; anoxia, 275 +/- 47; rasagiline-treated anoxia, 325 +/- 35. Results are mean +/- SD from each of seven to nine different donors in a group. Thus, improvement in memory and learning tasks of the rasagiline-treated anoxia group finds correspondence in the activity of the cholinergic marker ChAT in two brain regions that have prominent cholinergic innervation.
机译：雷沙吉兰（N-炔丙基-1（R）氨基茚满）是一种选择性有效的MAO-B抑制剂，目前正在开发为甲磺酸盐（TVP-1012），用于治疗各种神经系统疾病。对成年和衰老大鼠（正常或缺氧病变）的初步研究表明，雷沙吉兰的长期治疗可改善记忆和学习任务的表现，表明对中枢胆碱能功能有一些有益作用。我们现在已经使用产后缺氧损伤的大鼠作为胆碱能功能障碍的模型。在新生大鼠中，缺氧强烈影响胆碱能系统，在这种生命状态下，胆碱能系统尚未完全成熟。从第1天到研究结束（第60天），首先通过哺乳母乳直至断奶（第21天），然后在饮用水中以0.5 mg / kg /天的速率施用甲磺酸雷沙吉兰。通过分析大脑中MAO活性（在21天时）验证了药物能否进入中枢神经系统。治疗改善了与缺氧有关的青少年多动症（第28天）。它将被动回避测试的性能提高到了正常对照水平（第40天）。它将莫里斯水迷宫中的空间记忆性能提高到了正常控制水平（第50天）。未经治疗的缺氧组无法完成这些任务，并且显着低于正常对照组和雷沙吉兰治疗的缺氧组。测定这些组中每组大鼠尾状和海马中的ChAT活性，得出以下结果（pmol ACh / mg蛋白质/ min）。尾状：正常对照，588 +/- 56;缺氧，398 +/- 54;雷沙吉兰治疗的缺氧，536 +/-35。海马：正常对照，380 +/- 31;缺氧，275 +/- 47;雷沙吉兰治疗的缺氧，325 +/-35。结果是一组中七个至九个不同供体各自的平均值+/- SD。因此，雷沙吉兰治疗的缺氧组的记忆力和学习任务的改善在胆碱能神经支配的两个大脑区域中发现了胆碱能标志物ChAT的活性。

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