Zhang Xiaofan, Li Qi, Wong Naikei, Zhang Min, Wang Wei, Bu Bitao, McAlonan Grainne Mary
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), China; Department of Psychiatry, University of Hong Kong, Hong Kong Special Administrative Region.
Department of Psychiatry, University of Hong Kong, Hong Kong Special Administrative Region.
Brain Res Bull. 2015 Jul;116:16-24. doi: 10.1016/j.brainresbull.2015.05.003. Epub 2015 May 21.
Experimental animals provide valuable opportunities to establish aetiological mechanisms and test new treatments for neurodevelopmental psychiatric conditions. However, it is increasingly appreciated that inter-strain differences cannot be neglected in the experimental design. In addition, the importance of including females in preclinical - but also clinical - research is now recognised. Here, we compared behaviour and prefrontal protein differences in male and female C57BL/6N and 129X1/SvJ mice as both are commonly used experimental rodents. Relative to 129X1/SvJ mice, both sexes of C57BL/6N mice had weaker sensorimotor gating, measured in the prepulse inhibition (PPI) of startle paradigm, and were more sensitive to amphetamine challenge in the open field. The pattern of protein expression in the prefrontal cortex of C57BL6N mice was also clearly distinct from 129X1/SvJ mice. Proteins differentially expressed were those associated with oxidative metabolism, receptor protein signalling, cell communication and signal transduction and energy pathways. We suggest that the C57BL/6N mouse may usefully proxy features of the neurodevelopmental disorders and could have application in pre-translational screening of new therapeutic approaches. The 129X1/SvJ strain in contrast, might be better suited to experimental studies of causal risk factors expected to lower PPI and increase amphetamine sensitivity.
实验动物为建立神经发育性精神疾病的病因机制和测试新疗法提供了宝贵机会。然而,人们越来越认识到在实验设计中不能忽视品系间差异。此外,目前已认识到在临床前研究以及临床研究中纳入雌性动物的重要性。在此,我们比较了雄性和雌性C57BL/6N小鼠与129X1/SvJ小鼠的行为及前额叶蛋白差异,因为这两种都是常用的实验啮齿动物。相对于129X1/SvJ小鼠,C57BL/6N小鼠的两性在惊吓范式的前脉冲抑制(PPI)中测量到的感觉运动门控较弱,并且在旷场中对苯丙胺激发更为敏感。C57BL6N小鼠前额叶皮质中的蛋白表达模式也明显不同于129X1/SvJ小鼠。差异表达的蛋白与氧化代谢、受体蛋白信号传导、细胞通讯以及信号转导和能量途径相关。我们认为C57BL/6N小鼠可能有助于模拟神经发育障碍的特征,并可应用于新治疗方法的临床前筛选。相比之下,129X1/SvJ品系可能更适合于对预期会降低PPI并增加苯丙胺敏感性的因果风险因素进行实验研究。