Low-Dose Homocystine Enhances Proliferation and Migration of Bv2 Microglia Cells

Homocysteine (Hcy) is a non-essential amino acid that is derived from the breakdown of dietary methionine. Hyperhomocysteinemia (HHcy) is an independent risk factor for a variety of chronic diseases, especially neurodegenerative conditions. To better understand the role of HHcy in the pathogenesis of neurodegenerative disorders, we investigated the effect of Hcy on the proliferation and activation of microglia Bv2 cells. Cells were treated with six different Hcy concentrations: 0, 50, 100, 300, 500, and 1000 A mu M for different time periods (8, 12, 16, 24, and 48 h). The morphology of Bv2 cells was observed, and cell activity and proliferation were detected. Cell migration and secretion of pro-inflammatory cytokines were detected by the scratch wound assay, the transwell assay, and ELISA, respectively. The effect of Hcy on Bv2 proliferation occurred earlier (< 24 h, especially 16 h) after treatment with concentrations between 100 and 300 mu M, and there was no cytotoxicity to Bv2 cells. Meanwhile, functional assays suggested that Hcy not only promoted Bv2 secretion of the pro-inflammatory cytokines IL-1 beta, TNF-alpha, and IL-6, but also enhanced Bv2 migration and invasion, with 100 mu M being the most effective concentration. In summary, Bv2 proliferation and activation can be promoted by short-term treatment with low-dose Hcy.