Aim: 

Although the role of 1a,25-dihydroxyvitamin D3 (VitD3) in the homeostasis of Ca²⁺ and phosphate is well known, its role in brain function is less clear.

In the present work we have studied whether VitD3 modulate the death and survival of differentiated SH-SH5H cells in response to beta amyloid (Abeta) peptide and the involvement of ceramide and sphingosine-1-phosphate (S1P) in hormone action.

Methods: 

After treatment of differentiated SH-SY5Y cells with vitD3 and/or Abeta peptide, caspase-3 activity and sphingosine kinase activity have been measured while expression of cell death-marker proteins have been analysed by Western blotting.

Results: 

We found that both VitD3 and Abeta peptide induced cell growth arrest, as judged by Western analysis and caspase-3 activity, and markedly down-regulated sphingosine kinase activity. However, when VitD3 was added to the cell medium before Abeta peptide treatment, the pro-apoptotic effect was significantly reduced, suggesting a neuroprotective effect of VitD3 on the citotoxicity induced by the Abeta peptide. Notably, although both agonists reduced the synthesis of the pro-survival factor S1P, VitD3 could prevent Abeta peptide-induced toxicity affecting ceramide content.

Conclusion: 

Taken together, these results provide the first evidence of the ability of VitD3 to prevent the neurodegeneration upon Abeta treatment through the regulation of ceramide/S1P ratio, critical determinant of death and survival in SH-SY5Y differentiated cells.