Effects of Dietary Vitamin D Levels on Markers Related to Amyloidogenesis and Neuroinflammation in db/db Mice

TL;DR

This study shows that high vitamin D diets may protect brain regions in diabetic mice by reducing harmful amyloid and inflammation markers.

Contribution

The study reveals that dietary vitamin D reduces amyloidogenic and inflammatory gene expression in diabetic mice brains.

Findings

High vitamin D diets reduced neuronal necrosis and amyloidogenic gene expression in diabetic mice.

Diabetic mice on high vitamin D diets showed lower inflammation-related gene expression.

Aβ42 protein levels remained unaffected by vitamin D or diabetes.

Abstract

Background/Objectives: Low vitamin D levels are associated with an elevated risk of Alzheimer’s disease (AD). Given the rising prevalence of diabetes and its association with AD, this study investigated whether vitamin D modulates amyloidogenesis and inflammation in the brains of diabetic mice. Methods: Five-week-old male C57BLKS/J-m+/m+(con) and C57BLKS/J-db/db (db) mice received diets with low or high vitamin D (LVD or HVD) for 8 weeks. Hippocampal neuronal morphology was assessed using H&E and Nissl staining, and Aβ levels, along with the mRNA expression of genes related to amyloidogenesis, amyloid degradation, inflammation, antioxidation, and neurotrophic factors, were measured in the hippocampus and prefrontal cortex (PFC). Results: High dietary vitamin D levels attenuated neuronal necrosis in db/db mice. Hippocampal App and Bace1 expression levels were higher in db/db mice; however, amyloidogenic gene (App, Bace1, Ps1) expression levels in both the hippocampus and PFC were significantly lower in db_HVD group compared with those in db_LVD group (all p < 0.05). Among control mice, PFC App and Ps1 expression levels were lower in con_HVD group than in con_LVD group. Nonetheless, Aβ42 protein levels were not affected by either diabetes or dietary vitamin D levels. Furthermore, lower hippocampal Iκbα and PFC Mcp-1 expression levels in db_HVD group than those in db_LVD group were observed, both upregulated in diabetic mice. Amyloid degradation-related gene or Vdr expression was not altered by dietary vitamin D levels. Conclusions: These findings suggest that vitamin D may exert neuroprotective effects on the hippocampus and PFC in diabetic mice by mitigating neuronal damage and suppressing amyloidogenic and inflammatory gene expression.

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