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Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats

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Research Article: Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats
Author: Sarawut Lapmanee, Sakkarin Bhubhanil, Siriwan Sriwong, Chaowalit Yuajit, Prapimpun Wongchitrat, Jarinthorn Teerapornpuntakit, Panan Suntornsaratoon, Jantarima Charoenphandhu, Narattaphol Charoenphandhu
Email: sarawut.lap@siam.edu  ;  sakkarin.bhu@siam.edu
Department|Faculty: Faculty of Medicine,  Siam University, Bangkok 10160
Published: PLoS One, 2023 Aug 11, 18(8), e0290106. doi: 10.1371/journal.pone.0290106. eCollection 2023

Citation

Lapmanee S., Bhubhanil S., Sriwong S., Yuajit C., Wongchitrat P., Teerapornpuntakit J., Suntornsaratoon P., Charoenphandhu J., Charoenphandhu N. (2023). Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats. PLoS One, 18(8), e0290106. doi: 10.1371/journal.pone.0290106


ABSTRACT

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.


Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats

Faculty of Medicine, Siam University, Bangkok, Thailand