| First Author | Guo YX | Year | 2016 |
| Journal | Neuroscience | Volume | 322 |
| Pages | 28-38 | PubMed ID | 26820600 |
| Mgi Jnum | J:235813 | Mgi Id | MGI:5803749 |
| Doi | 10.1016/j.neuroscience.2016.01.041 | Citation | Guo YX, et al. (2016) 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Abeta1-40 brain-to-blood efflux and peripheral uptake transport. Neuroscience 322:28-38 |
| abstractText | Alzheimer's disease (AD) is characterized by the accumulation and deposition of plaques of amyloid-beta (Abeta) peptide in the brain. Growing epidemiological and experimental studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts neuroprotection against AD. However, the underlying mechanisms of the action remain unclear. Since Abeta clearance plays a crucial role in Abeta balance in the brain, the aim of the present study was to investigate potential effects of 1,25(OH)2D3 on Abeta1-40, the major soluble oligomeric form of Abeta, clearance via transport across blood-brain barrier (BBB) mediated by low-density lipoprotein receptor-related protein 1 (LRP1) (efflux) and receptor for advanced glycation end products (RAGE) (influx) and peripheral uptake by liver mediated by LRP1. We identified colocalization of LRP1 and RAGE at BBB of mice, established an in vitro BBB model by culturing monolayer mouse brain microvascular endothelial cell line (bEnd.3) cells under hypoxia and observed that 1,25(OH)2D3 treatment enhanced Abeta1-40 efflux across the BBB model and uptake by HepG2 cells. After 1,25(OH)2D3 exposure, LRP1 expression was increased significantly both in vivo and in vitro, and RAGE expression was reduced in the in vitro BBB model but not in microvascular endothelial cells of mice hippocampus. Additionally, we explored the correlation between the corresponding effects of 1,25(OH)2D3 and its nuclear hormone receptor vitamin D receptor (VDR) level. We found that VDR expression was upregulated after 1,25(OH)2D3 treatment both in vivo and in vitro. Collectively, our finding that 1,25(OH)2D3 reduces cerebral Abeta1-40 level by increasing Abeta1-40 brain-to-blood efflux and peripheral uptake through regulating LRP1 and RAGE could shed light on the mechanism of 1,25(OH)2D3 neuroprotection against AD. And the action of 1,25(OH)2D3 might be associated with the VDR pathway. |
