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Combining the lack of chromogranins with chronic L-DOPA treatment affects motor activity in mice
Cell and Tissue Research ( IF 3.2 ) Pub Date : 2020-01-03 , DOI: 10.1007/s00441-019-03159-8
Leandro Castañeyra-Ruiz , Agustín Castañeyra , Ayoze González-Santana , José D. Machado , Ricardo Borges

We have tested whether the lack of chromogranins (Cgs) A and B could provoke CNS disorders when combined with an excess of dopamine. We chronically treated (over 6 months) mice lacking both chromogranins A and B (Cgs-KO) with a low oral dosage of L-DOPA/benserazide (10/2.5 mg/kg). Motor performance in the rota-rod test, open field activity, and metabolic cages indicated a progressive impairment in motor coordination in these mice, and an increase in rearing behavior, which was accompanied by an increase in DA within the substantia nigra. We conclude that mild chronic L-DOPA treatment does not produce nigro-striatal toxicity that could be associated with parkinsonism, neither in control nor Cgs-KO mice. Rather, Cgs-KO mice exhibit behaviors compatible with an amphetamine-like effect, probably caused by the excess of catecholamines in the CNS.

中文翻译:

将嗜铬粒蛋白的缺乏与慢性左旋多巴治疗相结合会影响小鼠的运动活动

我们已经测试了缺乏嗜铬粒蛋白 (Cgs) A 和 B 在与过量多巴胺结合时是否会引起中枢神经系统疾病。我们用低剂量的左旋多巴/苄丝肼 (10/2.5 mg/kg) 长期治疗(超过 6 个月)缺乏嗜铬粒蛋白 A 和 B (Cgs-KO) 的小鼠。旋转杆试验、野外活动和代谢笼中的运动表现表明这些小鼠的运动协调性逐渐受损,饲养行为增加,伴随着黑质内 DA 的增加。我们得出结论,无论是在对照小鼠还是 Cgs-KO 小鼠中,轻度慢性左旋多巴治疗都不会产生可能与帕金森症相关的黑质纹状体毒性。相反,Cgs-KO 小鼠表现出与苯丙胺样作用相容的行为,这可能是由中枢神经系统中过量的儿茶酚胺引起的。
更新日期:2020-01-03
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