Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Interdisciplinary Neurobehavioral Core, Heidelberg University, Heidelberg, Germany.
Sci Rep. 2021 Mar 22;11(1):6497. doi: 10.1038/s41598-021-85858-3.
Neuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. Although the onset of many neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and attention-deficit hyperactivity disorder emerges mainly during infancy and adolescence, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, possibly missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we examined which behavioral tests assessing both motor and coordination functions can be performed in mice at two different adolescent stages. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N. Adolescent mice of both postnatal days (P)22-30 and P32-40 developmental stages were capable of mastering common motor and coordination tests. However, results differed significantly between strains and sexes. Moreover, the 10-day interval between the two tested cohorts uncovered a strong difference in the behavioral results, confirming the significant impact of maturation on behavioral patterns. Interestingly, the results of distinct behavioral experiments were directly correlated with the weight of mice, which may explain the lack of reproducibility of some behavioral results in genetically-modified mice. Our study paves the way for better reproducibility of behavioral tests by addressing the effect of the developmental stage, strain, sex, and weight of mice on achieving the face validity of neuropsychiatric disorder-associated motor dysfunctions.
神经精神疾病通常与运动和协调异常有关,这些异常对这些疾病的病因、病理生理学和治疗有重要影响。尽管许多神经精神疾病的发病,包括自闭症谱系障碍、精神分裂症和注意缺陷多动障碍,主要发生在婴儿期和青少年期,但大多数模拟神经精神表型的小鼠模型的行为研究都是在成年动物中进行的,这可能会错过与发育过程中突触成熟相关的有价值的表型信息。在这里,我们研究了哪些评估运动和协调功能的行为测试可以在两个不同的青少年阶段在小鼠中进行。由于品系和性别会影响小鼠的行为,我们的实验涵盖了三种近交野生型品系(C57BL/6N、DBA/2 和 FVB/N)的雄性和雌性小鼠。出生后第 22-30 天和第 32-40 天的青少年小鼠都能够掌握常见的运动和协调测试。然而,结果在品系和性别之间存在显著差异。此外,两个测试组之间的 10 天间隔期揭示了行为结果之间的显著差异,证实了成熟对行为模式的显著影响。有趣的是,不同行为实验的结果与小鼠的体重直接相关,这可能解释了一些遗传修饰小鼠的行为结果缺乏可重复性的原因。我们的研究通过解决发育阶段、品系、性别和体重对实现与神经精神障碍相关运动功能障碍的表面有效性的影响,为更好地重现行为测试铺平了道路。