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慢性运动和抗精神病药奥氮平治疗对成年雌性大鼠海马体积的影响。

Effects of chronic exercise and treatment with the antipsychotic drug olanzapine on hippocampal volume in adult female rats.

机构信息

Department of Pharmacology, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; British Columbia Mental Health & Addictions Research Institute, 938 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada.

出版信息

Neuroscience. 2013;255:147-57. doi: 10.1016/j.neuroscience.2013.10.010. Epub 2013 Oct 18.

Abstract

Numerous studies have reported that the hippocampus in schizophrenia patients is reduced in volume compared to the normal population. Antipsychotic medications have had mixed benefits in maintaining hippocampal volume or reversing volume loss. Recent evidence indicates that routine aerobic exercise represents a promising intervention for reversing hippocampal loss and cognitive deficits. In the present study, we measured the effects of chronic treatment with olanzapine and daily exercise on the hippocampal volumes of rats. Adult female rats were treated during the week with either olanzapine (10mg/kg) or vehicle for 9 consecutive weeks. Subgroups of animals were provided access to exercise running wheels for 1 or 3h per day during the same period, or were sedentary. Metabolic indices, including glucose tolerance, were measured on a weekly basis. At the conclusion of the study, brains were perfused and hippocampal sections were Nissl stained. Total hippocampal volume was measured using the Cavalieri estimator. Treatment with olanzapine caused a significant decrease in hippocampal volume in sedentary rats. However, exercise was able to reverse most of this volume loss. The hippocampal sub-regions of the dentate gyrus and CA1 were most strongly affected by olanzapine and exercise. Of interest, there was a strong and highly significant negative correlation between glucose intolerance and hippocampal volume, whereby greater glucose intolerance was associated with a smaller hippocampal volume. These findings indicate that exercise may have beneficial effects on the hippocampus when antipsychotic medication can contribute to changes in volume.

摘要

许多研究报告指出,与正常人群相比,精神分裂症患者的海马体体积减小。抗精神病药物在维持海马体体积或逆转体积损失方面的益处不一。最近的证据表明,常规的有氧运动是逆转海马体损失和认知缺陷的一种很有前途的干预手段。在本研究中,我们测量了慢性奥氮平治疗和日常运动对大鼠海马体体积的影响。成年雌性大鼠在连续 9 周内每周接受奥氮平(10mg/kg)或载体处理。在同一时期,部分动物可使用跑步轮进行 1 或 3 小时/天的运动,或保持久坐不动。每周测量代谢指标,包括葡萄糖耐量。在研究结束时,对大脑进行灌流,并用尼氏染色对海马切片进行染色。使用 Cavalieri 估计器测量总海马体体积。奥氮平处理使久坐不动的大鼠的海马体体积显著减小。然而,运动能够逆转大部分的体积损失。齿状回和 CA1 的海马亚区受奥氮平和运动的影响最大。有趣的是,葡萄糖耐量与海马体体积之间存在强烈且高度显著的负相关,即葡萄糖耐量越大,海马体体积越小。这些发现表明,当抗精神病药物可能导致体积变化时,运动可能对海马体有有益的影响。

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