Department of Basic Medical Sciences, Faculty of Medicine, Siam University, Bangkok, Thailand.
Laboratory Animal Center, Thammasat University, Pathum Thani, Thailand.
PLoS One. 2023 Aug 11;18(8):e0290106. doi: 10.1371/journal.pone.0290106. eCollection 2023.
Oral calcium and calcium plus vitamin D supplements are commonly prescribed to several groups of patients, e.g., osteoporosis, fracture, and calcium deficiency. Adequate and steady extracellular calcium levels are essential for neuronal activity, whereas certain forms of calcium supplement (e.g., CaCO3) probably interfere with memory function. However, it was unclear whether a long-term use of ionized calcium (calcium chloride in drinking water ad libitum), vitamin D supplement (oral gavage) or the combination of both affected anxiety and memory, the latter of which was probably dependent on the hippocampal neurogenesis. Here, we aimed to determine the effects of calcium and/or vitamin D supplement on the anxiety- and memory-related behaviors and the expression of doublecortin (DCX), an indirect proxy indicator of hippocampal neurogenesis. Eight-week-old male Wistar rats were divided into 4 groups, i.e., control, calcium chloride-, 400 UI/kg vitamin D3-, and calcium chloride plus vitamin D-treated groups. After 4 weeks of treatment, anxiety-, exploration- and recognition memory-related behaviors were evaluated by elevated pulse-maze (EPM), open field test (OFT), and novel object recognition (NOR), respectively. The hippocampi were investigated for the expression of DCX protein by Western blot analysis. We found that oral calcium supplement increased exploratory behavior as evaluated by OFT and the recognition index in NOR test without any effect on anxiety behavior in EPM. On the other hand, vitamin D supplement was found to reduce anxiety-like behaviors. Significant upregulation of DCX protein expression was observed in the hippocampus of both calcium- and vitamin D-treated rats, suggesting their positive effects on neurogenesis. In conclusion, oral calcium and vitamin D supplements positively affected exploratory, anxiety-like behaviors and/or memory in male rats. Thus, they potentially benefit on mood and memory in osteoporotic patients beyond bone metabolism.
口服钙剂和钙加维生素 D 补充剂常用于骨质疏松症、骨折和钙缺乏症等多种患者。足够且稳定的细胞外钙水平对神经元活动至关重要，而某些形式的钙补充剂（例如 CaCO3）可能会干扰记忆功能。然而，长期使用离子钙（饮用水中自由添加的氯化钙）、维生素 D 补充剂（口服灌胃）或两者的组合是否会影响焦虑和记忆功能尚不清楚，后者可能依赖于海马神经发生。在这里，我们旨在确定钙和/或维生素 D 补充剂对焦虑和记忆相关行为以及双皮质蛋白 (DCX) 表达的影响，DCX 是海马神经发生的间接代理指标。8 周龄雄性 Wistar 大鼠分为对照组、氯化钙组、400 UI/kg 维生素 D3 组和氯化钙加维生素 D 组。治疗 4 周后，通过高架十字迷宫（EPM）、旷场试验（OFT）和新物体识别（NOR）分别评估焦虑、探索和识别记忆相关行为。通过 Western blot 分析研究海马中 DCX 蛋白的表达。我们发现，口服钙剂增加了 OFT 评估的探索性行为和 NOR 测试中的识别指数，而对 EPM 中的焦虑行为没有影响。另一方面，维生素 D 补充剂被发现可减少焦虑样行为。在钙和维生素 D 治疗的大鼠海马中观察到 DCX 蛋白表达的显著上调，表明它们对神经发生有积极影响。总之，口服钙和维生素 D 补充剂对雄性大鼠的探索性、焦虑样行为和/或记忆有积极影响。因此，它们可能有益于骨质疏松症患者的情绪和记忆，而不仅仅是骨骼代谢。
