Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
Eur J Neurosci. 2010 Feb;31(3):556-64. doi: 10.1111/j.1460-9568.2010.07074.x. Epub 2010 Jan 25.
Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia. A previous study in mice suggested that the offspring of aged sires have altered locomotion and avoidance learning. The aim of the current study was to conduct a comprehensive behavioural screen in adult offspring of mice of APA. We also examined brain morphology in neonate and adult mice. The adult offspring of 12- to 18-month-old (APA) and 4-month-old (control) male C57BL/6J mice underwent a behavioural test battery comprising tests for locomotion, anxiety, exploration, social behaviour, learned helplessness and sensorimotor gating. The brains of these mice were collected at 3 months and imaged ex vivo using a 16.4 T MRI scanner to assess gross neuroanatomy. Neuroanatomy was also examined at birth in a separate cohort of animals. Overall, the APA mouse model was associated with subtle behavioural changes and altered cortical morphology. The behavioural phenotype of female APA mice included increased anxiety-related behaviour, increased exploration and decreased learned helplessness compared to control females. Male APA mice had thinner cortices at birth and increased cortical volume as adults. This animal model may assist in exploring the mechanism of action linking APA with disorders such as schizophrenia and autism.
高龄父亲（Advanced Paternal Age，APA）与神经发育障碍（如自闭症和精神分裂症）的风险增加有关。先前在小鼠中的一项研究表明，老年雄鼠的后代运动和回避学习能力发生改变。本研究的目的是对 APA 雄鼠后代的成年鼠进行全面的行为筛查。我们还检查了新生和成年鼠的脑形态。12-18 月龄（APA）和 4 月龄（对照组）的 C57BL/6J 雄鼠的成年后代接受了行为测试，包括运动、焦虑、探索、社交行为、习得性无助和感觉运动门控测试。这些鼠的大脑在 3 个月时收集，并使用 16.4 T MRI 扫描仪进行离体成像，以评估大体神经解剖结构。在另一组动物中还检查了出生时的神经解剖结构。总体而言，APA 鼠模型与微妙的行为变化和皮质形态改变有关。与对照组雌性相比，APA 雌性的行为表型包括焦虑相关行为增加、探索增加和习得性无助减少。出生时，APA 雄鼠的皮质较薄，成年时皮质体积增加。这种动物模型可能有助于探索将 APA 与精神分裂症和自闭症等疾病联系起来的作用机制。
