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小檗碱对 MK-801 诱导的精神分裂症幼鼠模型认知和运动障碍的改善作用。

Ameliorating effects of berberine on MK-801-induced cognitive and motor impairments in a neonatal rat model of schizophrenia.

机构信息

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Neurosci Lett. 2019 Jul 27;706:151-157. doi: 10.1016/j.neulet.2019.05.029. Epub 2019 May 16.

Abstract

Neonatal administration of MK-801 (NMDA receptor antagonist) results in schizophrenia-like behaviors in rodents. Berberine (BBR) is a herbal alkaloid, which shows many neuroprotective properties in neurodegenerative diseases. The present study was designed to clarify whether systemic administration of BBR improves motor and cognitive disturbances induced by MK-801 treatment. Male Wistar rat pups were treated with intraperitoneal administration of saline (1 ml/kg) as a control group, MK-801 (1 mg/kg), BBR (20 mg/kg) and BBR (20 mg/kg) plus MK- 801 (1 mg/kg). Treatments were administered on postnatal day (P) 6-10 for once daily. To assess motor learning, coordination as well as spatial learning and memory, behavioral evaluation was performed at P55-60, using the rotarod, open field, and Morris water maze paradigm. MK-801 injection led to motor perturbations in both the open field and accelerating rotarod tests, which were restored by BBR. Also, BBR improved learning impairments, although it had no significant effect on the Probe test. Taken together, it can be concluded that BBR produces a neuroprotective effect in rats with MK-801-associated behavioral deficits. Given that the MK-801 exposure demonstrates an animal model of schizophrenia, we suggest that timely BBR administration may act as a potential treatment in schizophrenic patients.

摘要

新生鼠给予 MK-801(NMDA 受体拮抗剂)可导致类似精神分裂症的行为。小檗碱(BBR)是一种植物生物碱,在神经退行性疾病中显示出许多神经保护特性。本研究旨在阐明系统给予 BBR 是否能改善 MK-801 治疗引起的运动和认知障碍。雄性 Wistar 幼鼠接受腹腔内注射生理盐水(1ml/kg)作为对照组,MK-801(1mg/kg),BBR(20mg/kg)和 BBR(20mg/kg)加 MK-801(1mg/kg)。治疗在出生后第 6-10 天每天一次。为了评估运动学习、协调以及空间学习和记忆,在 P55-60 时使用转棒和开阔场地以及 Morris 水迷宫范式进行行为评估。MK-801 注射导致开阔场地和加速转棒测试中的运动扰动,BBR 可恢复这些运动扰动。此外,BBR 改善了学习障碍,尽管它对探测试验没有显著影响。综上所述,可以得出结论,BBR 对 MK-801 相关行为缺陷的大鼠具有神经保护作用。鉴于 MK-801 暴露表现出精神分裂症的动物模型,我们建议及时给予 BBR 可能是精神分裂症患者的潜在治疗方法。

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