Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
J Psychopharmacol. 2020 Jul;34(7):695-708. doi: 10.1177/0269881120922963. Epub 2020 May 20.
Cognitive impairment associated with schizophrenia (CIAS) greatly reduces patients' functionality, and remains an unmet clinical need. The sub-chronic phencyclidine (scPCP) rat model is commonly employed in studying CIAS. We have previously shown that voluntary exercise reverses impairments in novel object recognition (NOR) induced by scPCP. However, there has not been a longitudinal study investigating the potential protective effects of exercise in a model of CIAS. This study aimed to investigate the pro-cognitive and protective effects of exercise on CIAS using the translational NOR and attentional set-shifting tasks (ASST).
Female Lister Hooded rats were either exercised (wheel running for one hour per day, five days per week, for six weeks; =20) or not (=20) and then tested in a natural-forgetting NOR test. Rats in each group were then administered either PCP (2 mg/kg intraperitoneally (i.p.)) or saline solution (1 mL/kg i.p.) for seven days, followed by seven days washout. Three NOR tests were conducted immediately and two and nine weeks after washout, and a natural-forgetting NOR test was carried out again eight weeks post washout. Rats were trained and tested in ASST from week 6 to week 10 post washout.
Non-exercised rats displayed a deficit in both of the natural-forgetting NOR tests, whereas exercised rats did not. The scPCP exercise group did not show the expected deficit in NOR at any time point, and had a significantly ameliorated deficit in the ASST compared to the scPCP control group.
Voluntary exercise has long-lasting pro-cognitive and protective effects in two cognitive domains. Exercise improves cognition and could provide protection against CIAS.
与精神分裂症相关的认知障碍（CIAS）极大地降低了患者的功能，这仍然是未满足的临床需求。亚慢性苯环己哌啶（scPCP）大鼠模型常用于研究 CIAS。我们之前已经表明，自愿运动可以逆转 scPCP 引起的新物体识别（NOR）损伤。然而，目前还没有一项纵向研究调查运动对 CIAS 模型的潜在保护作用。本研究旨在使用转化的 NOR 和注意力定势转移任务（ASST）研究运动对 CIAS 的促认知和保护作用。
雌性 Lister Hooded 大鼠要么进行运动（每天运动一小时，每周五天，持续六周；=20），要么不运动（=20），然后在自然遗忘 NOR 测试中进行测试。每组大鼠随后连续七天接受 PCP（2mg/kg 腹腔内（i.p.））或生理盐水（1ml/kg i.p.）给药，然后进行七天洗脱期。在洗脱后立即进行三次 NOR 测试，两次和九周后进行测试，洗脱后八周再次进行自然遗忘 NOR 测试。大鼠在洗脱后第六周至第十周进行 ASST 训练和测试。
未运动的大鼠在两次自然遗忘 NOR 测试中均表现出缺陷，而运动的大鼠则没有。scPCP 运动组在任何时间点均未显示出预期的 NOR 缺陷，并且与 scPCP 对照组相比，ASST 中的缺陷明显改善。
自愿运动对两个认知领域具有持久的促认知和保护作用。运动可以改善认知，并且可以为预防 CIAS 提供保护。
