School of Human SciencesThe University of Western Australia, Perth, Australia.
Centre for MicroscopyCharacterisation and Analysis, The University of Western Australia, Perth, Australia.
J Endocrinol. 2018 May;237(2):73-85. doi: 10.1530/JOE-18-0008.
Early life vitamin D plays a prominent role in neurodevelopment and subsequent brain function, including schizophrenic-like outcomes and increasing evidence for an association with autism spectrum disorder (ASD). Here, we investigate how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring. Sprague-Dawley rats were placed on either a vitamin D control (2195 IU/kg) or deficient diet (0 IU/kg) for five weeks before timed mating, and diet exposure was maintained until weaning of offspring on postnatal day (PND) 23. MRI scans were conducted to assess brain morphology, and plasma corticosterone levels and neural expression of genes associated with language, dopamine and glucocorticoid exposure were characterised at PND1, PND12 and 4 months of age. Compared to controls, vitamin D-deficient dams exhibited decreased licking and grooming of their pups but no differences in pup retrieval. Offspring neurodevelopmental markers were unaltered, but vitamin D-deficient pup ultrasonic vocalisations were atypical. As adults, males that had been exposed to vitamin D deficiency in early life exhibited decreased social behaviour, impaired learning and memory outcomes and increased grooming behaviour, but unaltered affective behaviours. Accompanying these behavioural changes was an increase in lateral ventricle volume, decreased cortical FOXP2 (a protein implicated in language and communication) and altered neural expression of genes involved in dopamine and glucocorticoid-related pathways. These data highlight that early life levels of vitamin D are an important consideration for maternal behavioural adaptations as well as offspring neuropsychiatry.
生命早期的维生素 D 对神经发育和随后的大脑功能起着重要作用，包括类似精神分裂症的结果，并越来越多地证明与自闭症谱系障碍（ASD）有关。在这里，我们研究了妊娠和哺乳期大鼠生命早期维生素 D 缺乏如何改变母性行为，并影响雄性成年后代的神经发育以及情感、认知和社交行为。Sprague-Dawley 大鼠在进行定时交配前，连续五周分别接受维生素 D 对照（2195 IU/kg）或缺乏饮食（0 IU/kg），并在产后第 23 天（PND）断奶后继续暴露于饮食中。进行磁共振成像（MRI）扫描以评估大脑形态，检测血浆皮质酮水平，并在 PND1、PND12 和 4 月龄时检测与语言、多巴胺和糖皮质激素暴露相关的基因的神经表达。与对照组相比，维生素 D 缺乏的母鼠对其幼崽的舔舐和梳理行为减少，但幼崽的检索行为没有差异。后代神经发育标志物没有改变，但维生素 D 缺乏的幼鼠的超声波发声不典型。作为成年人，生命早期暴露于维生素 D 缺乏的雄性表现出社交行为减少、学习和记忆能力受损以及梳理行为增加，但情感行为没有改变。伴随着这些行为变化，侧脑室体积增加，皮质 FOXP2（一种与语言和交流有关的蛋白质）减少，以及参与多巴胺和糖皮质激素相关途径的基因的神经表达改变。这些数据表明，生命早期的维生素 D 水平是母体行为适应以及后代神经精神疾病的一个重要考虑因素。
