Horvath Gyongyi, Kekesi Gabriella, Petrovszki Zita, Benedek Gyorgy
Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Institute of Physical Education and Sport Medicine, Juhász Gyula Faculty of Education, University of Szeged, Szeged, Hungary.
PLoS One. 2015 Dec 2;10(12):e0143751. doi: 10.1371/journal.pone.0143751. eCollection 2015.
Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.
Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.
Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.
In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research.
精神分裂症伴有运动活动改变和体温调节异常;因此,这些症状的存在可以提高精神分裂症动物模型的表面效度。目的是在表现出几种与精神分裂症相关改变的新型大鼠亚系的自由活动状态下对这些参数进行表征。
使用雄性Wistar大鼠:将新亚系单独饲养(四周)并用氯胺酮进行亚慢性处理,以及未经任何处理的未处理动物。成年动物腹腔内植入E-Mitter应答器以连续记录体温和运动活动。在不受干扰的情况下分析这些参数的昼夜节律以及光照条件变化的急性影响,还确定了不同干预措施(处理、更换垫料或腹腔注射溶剂)的影响。
在新亚系中观察到运动活动减少且模式分散。然而,这些动物在活跃期体温较高,并且其变化范围也更广。光照条件的变化和不同干预措施在新亚系中产生了减弱的多动和改变的体温反应。体温的庞加莱图分析显示,与非活跃期相比,两组在活跃期的短期和长期变异性均增强。此外,新亚系显示短期和长期变异性增加,不对称程度较低,提示自主神经调节异常。
总之,具有精神分裂症相关现象的新亚系表现出运动活动和体温调节紊乱,表明这些客观确定的参数可以作为转化研究中的生物标志物。