Wong-Goodrich Sarah J E, Glenn Melissa J, Mellott Tiffany J, Blusztajn Jan K, Meck Warren H, Williams Christina L
Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA.
Brain Res. 2008 Oct 27;1237:153-66. doi: 10.1016/j.brainres.2008.08.074. Epub 2008 Sep 4.
Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then returned to a control diet (1.1 g choline chloride/kg). At 70 days of age, we found that DEF and SUP rats required fewer choices to locate 8 baited arms of a 12-arm radial maze than CON rats. When switched to a choline-deficient diet (0 g/kg), SUP rats showed impaired performance while CON and DEF rats were unaffected. In contrast, when switched to a choline-supplemented diet (5.0 g/kg), DEF rats' performance was significantly impaired while CON and SUP rats were less affected. These changes in performance were reversible when the rats were switched back to a control diet. In a second experiment, DEF, CON, and SUP rats were either maintained on a control diet, or the choline-supplemented diet. After 12 weeks, DEF rats were significantly impaired by choline supplementation on a matching-to-place water-maze task, which was also accompanied by a decrease in dentate cell proliferation in DEF rats only. IGF-1 levels were elevated by both prenatal and adult choline supplementation. Taken together, these findings suggest that the in utero availability of an essential nutrient, choline, causes differential behavioral and neuroplastic sensitivity to the adult choline supply.
生命早期饮食中胆碱可利用性的改变会导致成年期空间记忆和海马可塑性的持续变化。早期胆碱营养的发育编程可能决定了对认知功能所涉及的神经可塑性类型而言最佳的成年胆碱摄入量范围。为了验证这一点,在胚胎期第12至17天,将雄性斯普拉格-道利大鼠暴露于氯化胆碱缺乏(DEF)、充足(CON)或补充(SUP)饮食中,然后恢复到对照饮食(1.1克氯化胆碱/千克)。在70日龄时,我们发现DEF和SUP组大鼠在定位12臂放射状迷宫的8个诱饵臂时所需的选择次数比CON组大鼠少。当改为胆碱缺乏饮食(0克/千克)时,SUP组大鼠表现受损,而CON组和DEF组大鼠未受影响。相反,当改为胆碱补充饮食(5.0克/千克)时,DEF组大鼠的表现明显受损,而CON组和SUP组大鼠受影响较小。当大鼠换回对照饮食时,这些表现变化是可逆的。在第二个实验中,DEF、CON和SUP组大鼠要么维持对照饮食,要么维持胆碱补充饮食。12周后,在位置匹配水迷宫任务中,胆碱补充使DEF组大鼠明显受损,且仅在DEF组大鼠中伴有齿状细胞增殖减少。产前和成年期胆碱补充均使IGF-1水平升高。综上所述,这些发现表明,必需营养素胆碱在子宫内的可利用性导致了对成年胆碱供应的不同行为和神经可塑性敏感性。