Kang Jiseung, Park Mincheol, Lee Eunkyung, Jung Jieun, Kim Tae
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
Biomedicines. 2022 Jul 28;10(8):1824. doi: 10.3390/biomedicines10081824.
Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) accumulation and cognitive mental decline. Epidemiological studies have suggested an association between low serum vitamin D levels and an increased risk of AD. Vitamin D regulates gene expression via the vitamin D receptor, a nuclear ligand-dependent transcription factor. However, the molecular mechanism underlying the pathogenic and therapeutic effects of vitamin D on AD is not fully understood yet. To better understand how vitamin D regulates the expression of genes related to AD pathology, first, we induced vitamin D deficiency in 5xFAD mice by providing a vitamin-D-deficient diet and observed the changes in the mRNA level of genes related to Aβ processing, which resulted in an increase in the Aβ load in the brain. The vitamin D-deficient diet also suppressed the expression of genes for microglial Aβ phagocytosis. Interestingly, vitamin D deficiency in the early stage of AD resulted in earlier memory impairment. In addition, we administered vitamin D intraperitoneally to 5xFAD mice with a normal diet and found lower Aβ levels with the suppressed expression of genes for Aβ generation and observed improved memory function, which may be potentially associated with reduced MAO-B expression. These findings strongly suggest the role of vitamin D as a crucial disease-modifying factor that may modulate the amyloid pathology with regard to reducing AD symptoms.
阿尔茨海默病（AD）的特征是β淀粉样蛋白（Aβ）积累和认知功能衰退。流行病学研究表明，血清维生素D水平低与AD风险增加之间存在关联。维生素D通过维生素D受体调节基因表达，维生素D受体是一种核配体依赖性转录因子。然而，维生素D对AD的致病和治疗作用的分子机制尚未完全明确。为了更好地了解维生素D如何调节与AD病理相关的基因表达，首先，我们通过提供维生素D缺乏饮食在5xFAD小鼠中诱导维生素D缺乏，并观察与Aβ加工相关基因的mRNA水平变化，这导致大脑中Aβ负荷增加。维生素D缺乏饮食还抑制了小胶质细胞Aβ吞噬相关基因的表达。有趣的是，AD早期的维生素D缺乏导致更早的记忆障碍。此外，我们对正常饮食的5xFAD小鼠腹腔注射维生素D，发现Aβ水平降低，Aβ生成相关基因的表达受到抑制，并观察到记忆功能改善，这可能与单胺氧化酶B（MAO-B）表达降低有关。这些发现有力地表明维生素D作为一种关键的疾病修饰因子的作用，它可能通过调节淀粉样蛋白病理来减轻AD症状。
