Harms Lauren R, Eyles Darryl W, McGrath John J, Mackay-Sim Alan, Burne Thomas H J
School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Behav Brain Res. 2008 Mar 5;187(2):343-50. doi: 10.1016/j.bbr.2007.09.032. Epub 2007 Oct 5.
Developmental vitamin D (DVD) deficiency has been proposed as an environmental risk factor for a number of brain disorders. The absence of this vitamin during foetal development in the rat is known to alter behaviour in the adult, and many of these alterations are informative with respect to the clinical features of schizophrenia. Here we investigated whether DVD deficiency had a similar effect on 129/SvJ and C57BL/6J mice. Female mice were fed a diet deficient in vitamin D for 6 weeks prior to conception until birth, after which dams and their offspring were fed a normal diet (i.e. containing vitamin D). Control mice were fed a normal diet throughout the experiment. The adult offspring underwent a comprehensive behavioural test battery at 10 weeks of age. We found that DVD-deficient mice of both strains exhibited significantly higher levels of exploration, as measured by the frequency of head dipping on the hole board test. In addition, DVD-deficient 129/SvJ mice, but not C57BL/6J mice, displayed spontaneous hyperlocomotion. There was no effect of maternal diet on parameters assessed by the SHIRPA primary screen, or on tests of sensorimotor gating, social behaviour, anxiety or depression. Some of these findings resemble the rat phenotype (hyperlocomotion) but there are also novel effects of DVD deficiency on mouse behaviour (increased exploration). This study confirms that the developmental absence of this vitamin affects brain function in another species (mouse), and lends further weight to the hypothesis that DVD deficiency in humans may contribute to adverse neuropsychiatric outcomes.
发育性维生素D(DVD)缺乏已被认为是多种脑部疾病的环境风险因素。已知大鼠在胎儿发育期间缺乏这种维生素会改变成年后的行为,其中许多改变与精神分裂症的临床特征相关。在此,我们研究了DVD缺乏对129/SvJ和C57BL/6J小鼠是否有类似影响。雌性小鼠在受孕前6周直至分娩期间喂食缺乏维生素D的饮食,之后母鼠及其后代喂食正常饮食(即含有维生素D)。对照小鼠在整个实验过程中喂食正常饮食。成年后代在10周龄时接受了一系列全面的行为测试。我们发现,两种品系的DVD缺乏小鼠在洞板试验中通过头部探洞频率测量的探索水平显著更高。此外,DVD缺乏的129/SvJ小鼠而非C57BL/6J小鼠表现出自发性运动亢进。母体饮食对通过SHIRPA初级筛查评估的参数,或对感觉运动门控、社交行为、焦虑或抑郁测试均无影响。其中一些发现类似于大鼠表型(运动亢进),但DVD缺乏对小鼠行为也有新的影响(探索增加)。这项研究证实了这种维生素在发育过程中的缺乏会影响另一个物种(小鼠)的脑功能,并进一步支持了人类DVD缺乏可能导致不良神经精神后果的假说。