Biedermann Sarah V, Auer Matthias K, Bindila Laura, Ende Gabriele, Lutz Beat, Weber-Fahr Wolfgang, Gass Peter, Fuss Johannes
Department of Neuroimaging, Central Institute of Mental Health, University Medicine Mannheim, University of Heidelberg, 68159 Mannheim, Germany; Department of Psychiatry and Psychotherapy, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Horm Behav. 2016 Nov;86:45-54. doi: 10.1016/j.yhbeh.2016.09.007. Epub 2016 Sep 20.
Beneficial effects of voluntary wheel running on hippocampal neurogenesis, morphology and hippocampal-dependent behavior have widely been studied in rodents, but also serious side effects and similarities to stereotypy have been reported. Some mouse strains run excessively when equipped with running wheels, complicating the comparability to human exercise regimes. Here, we investigated how exercise restriction to 6h/day affects hippocampal morphology and metabolism, stereotypic and basal behaviors, as well as the endocannabinoid system in wheel running C57BL/6 mice; the strain most commonly used for behavioral analyses and psychiatric disease models. Restricted and unrestricted wheel running had similar effects on immature hippocampal neuron numbers, thermoregulatory nest building and basal home-cage behaviors. Surprisingly, hippocampal gray matter volume, assessed with magnetic resonance (MR) imaging at 9.4 Tesla, was only increased in unrestricted but not in restricted runners. Moreover, unrestricted runners showed less stereotypic behavior than restricted runners did. However, after blockage of running wheels for 24h stereotypic behavior also increased in unrestricted runners, arguing against a long-term effect of wheel running on stereotypic behavior. Stereotypic behaviors correlated with frontal glutamate and glucose levels assessed by H-MR spectroscopy. While acute running increased plasma levels of the endocannabinoid anandamide in former studies in mice and humans, we found an inverse correlation of anandamide with the daily running distance after long-term running. In conclusion, although there are some diverging effects of restricted and unrestricted running on brain and behavior, restricted running does not per se seem to be a better animal model for aerobic exercise in mice.
自愿性转轮运动对啮齿动物海马神经发生、形态及海马依赖性行为的有益影响已得到广泛研究，但也有严重副作用及与刻板行为相似性的报道。一些小鼠品系在配备转轮后会过度奔跑，这使得与人类运动模式的可比性变得复杂。在此，我们研究了将运动限制在每天6小时对转轮运动的C57BL/6小鼠（行为分析和精神疾病模型最常用的品系）海马形态和代谢、刻板行为和基础行为以及内源性大麻素系统的影响。受限和不受限的转轮运动对未成熟海马神经元数量、体温调节性筑巢及基础笼内行为有相似影响。令人惊讶的是，用9.4特斯拉磁共振成像评估的海马灰质体积仅在不受限的跑步者中增加，而在受限跑步者中未增加。此外，不受限的跑步者比受限跑步者表现出更少的刻板行为。然而，在转轮被阻塞24小时后，不受限跑步者的刻板行为也增加了，这表明转轮运动对刻板行为没有长期影响。刻板行为与通过氢磁共振波谱评估的额叶谷氨酸和葡萄糖水平相关。虽然在之前对小鼠和人类的研究中，急性跑步会增加内源性大麻素花生四烯乙醇胺的血浆水平，但我们发现长期跑步后花生四烯乙醇胺与每日跑步距离呈负相关。总之，尽管受限和不受限跑步对大脑和行为有一些不同影响，但受限跑步本身似乎并不是小鼠有氧运动的更好动物模型。
