O'Loan Jonathan, Eyles Darryl W, Kesby James, Ko Pauline, McGrath John J, Burne Thomas H J
Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Qld. 4076, Australia.
Psychoneuroendocrinology. 2007 Apr;32(3):227-34. doi: 10.1016/j.psyneuen.2006.12.006. Epub 2007 Feb 5.
Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley rats, their offspring were subjected to four different prenatal vitamin D conditions: (a) control (normal vitamin D throughout gestation); (b) early-DVD deficiency; (c) late-DVD deficiency; and (d) full-DVD deficiency. We show that the standard measure for vitamin D status, 25(OH)D(3), can be significantly manipulated within 7 days by dietary intervention. We also show that levels of the active form of this vitamin, 1,25(OH)(2)D(3), replete within the same time frame as 25(OH)D(3) but are slower to deplete. Developmental milestones remained normal across all four dietary groups. Concerning the adult behavioural phenotype, both full- and late-DVD deficiency were associated with MK-801-induced hyperlocomotion. Overall, these data suggest that vitamin D deficiency restricted to late gestation only is sufficient to disrupt adult brain functioning in the rat. These findings suggest there may be a therapeutic window for maternal dietary intervention in the DVD model of psychosis.
发育性维生素D（DVD）缺乏会改变大鼠的大脑发育和行为。本研究的目的是在妊娠期改变维生素D缺乏水平，并研究其对成年后代发育里程碑和行为的影响。通过对雌性斯普拉格-道利大鼠饮食中维生素D的撤减和重新添加进行操控，它们的后代经历了四种不同的产前维生素D状况：（a）对照组（整个妊娠期维生素D正常）；（b）早期DVD缺乏；（c）晚期DVD缺乏；以及（d）完全DVD缺乏。我们发现，通过饮食干预可在7天内显著操控维生素D状态的标准指标25(OH)D(3)。我们还发现，这种维生素的活性形式1,25(OH)₂D₃的水平在与25(OH)D₃相同的时间框架内恢复，但消耗较慢。所有四个饮食组的发育里程碑均保持正常。关于成年行为表型，完全和晚期DVD缺乏均与MK-801诱导的运动亢进有关。总体而言，这些数据表明，仅在妊娠晚期出现的维生素D缺乏就足以扰乱大鼠成年后的脑功能。这些发现表明，在精神分裂症的DVD模型中，母体饮食干预可能存在一个治疗窗口。
