Vitamin D Prevents Cognitive Decline and Enhances Hippocampal Synaptic Function in Aging Rats

Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.维生素D（Vitamin D）是一种重要的钙调节激素，在包括大脑在内的诸多组织中具有多样生物学功能。越来越多的研究证据表明，维生素D可能在维持认知功能中发挥作用，而维生素D缺乏则可能加速与年龄相关的认知衰退。本研究采用衰老啮齿类动物，构建了从缺乏到充足的人体血清维生素D水平梯度模型，以验证维生素D是否可在衰老进程中维持或改善认知功能。将中年F344大鼠分为三组，分别饲喂低、中（常规剂量）或高剂量维生素D3（Vitamin D3，分别为100、1000、10000 IU/kg日粮），持续5至6个月；随后通过莫里斯水迷宫（Morris water maze）检测海马依赖性学习与记忆能力。饲喂高剂量维生素D3的大鼠血清维生素D水平达到充足范围的最高值，且在莫里斯水迷宫反转实验这一可检测记忆细微变化的高难度任务中，表现显著优于低剂量与中剂量组大鼠。除钙相关通路外，海马基因表达芯片分析显示，高剂量维生素D3可上调与突触传递、细胞通信及G蛋白（G-protein）功能相关的信号通路。基础突触传递功能同样得到增强，佐证了此前关于基因表达与学习记忆的观测效应。本研究证实了维生素D营养状态与认知功能之间存在因果关系，并表明维生素D介导的海马基因表达变化或许可提升大脑健康衰老的可能性。