Browsing by Subject "calcium depletion"

Microglia, the resident immune cells of the central nervous system, react to inflammatory stimuli in the brain in a variety of ways. These include migrating to the site of damage and releasing pro- and anti-inflammatory factors. Previous research indicates that these microglial functions require extensive intracellular calcium signaling. Microglial overactivation can exacerbate neuronal damage, especially in cases of chronic inflammation. The ability to modulate the microglial response to damage would therefore be of great clinical relevance. The endoplasmic reticulum (ER) acts as the cell’s main calcium store and regulates cellular calcium levels primarily through the activity of ryanodine receptors (RYR), inositol-triphosphate receptors (IP3R), and the sarco-endoplasmic reticulum calcium ATPase (SERCA) pump. Calcium depletion from the ER is associated with cellular stress and microglial reactivity and therefore the ER may be an important target for modulating the microglial reactive response. The aim of this study is to show whether ER calcium depletion in a microglial cell line causes changes in protein expression, cellular infiltration, and the release of key pro-inflammatory factors. Drugs that block the pumping of calcium from the cytosol via the SERCA pump, such as thapsigargin, effectively induce a state of calcium depletion in the ER. In the present study, treatment with the SERCA pump inhibitor thapsigargin was found to increase SERCA2 expression in BV2, but not SV40, microglial cell lines. Treatment of microglia with thapsigargin was associated with large increases in the release of pro-inflammatory factors IL-6 and TNF-alpha but had no effect on microglial migration.