(P25-028-24) The Effects of Dietary Vitamin D Supplementation on Markers Related to Amyloidgenesis and Neuroinflammation in db/db Mice

Objectives: Vitamin D deficiency is associated with an increased risk of Alzheimer’s Disease (AD). With diabetes becoming more prevalent with age and its association with AD, this study aims to investigate whether vitamin D could affect amyloidogenesis and inflammation markers in diabetic mice.

Methods: Five-wk old male db/m+ and db/db mice were fed diets containing either low or high vitamin D (1,000 or 10,000 IU/kg diet) for 8 wks (CON_low, CON_high, DB_low, DB_high). H&E staining and Nissl staining were used to examine morphological changes in hippocampal neurons. The mRNA levels of genes related to amyloidogenesis (APP, BACE1, PS1), inflammatory responses (TNF-a, IL-6, IkBa, MCP1), antioxidant (NRF2, HO-1), and VDR in hippocampus and prefrontal cortex (PFC) were measured by real-time PCR.

Results: Overall, dietary vitamin D in DB mice showed a protective effect on neuronal necrosis. Both H&E and Nissl staining revealed neuronal necrosis in the hippocampus of the DB_low; however, the density of necrotic neurons was decreased in the DB_high. In the hippocampus of the DB_low, there was a significant increase in mRNA expression levels of APP and PS1, compared to the CON_low (all P < 0.05). However, in the hippocampus of the DB_high, the expression of APP, PS1, and BACE1 exhibited a reduction compared to the DB_low (all P < 0.05). Similarly, the mRNA levels of APP, PS1, and BACE1 in the PFC were significantly lower in the DB_high than in the DB_low. In addition, DB_high showed significantly lower levels of hippocampal IkBa and PFC MCP-1, when compared to the DB_low; while, the expression levels of IkBa and MCP-1 in the hippocampus and TNF-a, IkBa, and MCP-1 in the PFC were significantly elevated in DB_low compared to the CON_low. On the other hand, there was no significant difference in the gene expression of antioxidant markers and VDR in hippocampus in response to vitamin D or the presence of type 2 diabetes.

Conclusions: These findings suggest that vitamin D may play a neuroprotective role within the hippocampus of diabetic mice by recovering damaged neurons and reducing amyloidogenesis. Additionally, vitamin D alleviated inflammatory responses induced by type 2 diabetes in the hippocampus and PFC.

Funding Sources: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2021R1G1A1093362, 2021R1A2C2012013).