Pharmacological stimulation of sigma-1 receptor promotes activation of astrocyte via ERK1/2 and GSK3β signaling pathway

Astrocyte is considered to be a type of passive supportive cells that preserves neuronal activity and survival. The dysfunction of astrocytes is involved in the pathological processes of major depression. Recent studies implicate sigma-1 receptors as putative therapeutic targets for current available antidepressant drugs. However, it is absent of direct evidences whether sigma-1 receptor could promote activation of astrocyte. In the present study, we took advantage of primary astrocyte culture and a highly selective agonist of sigma-1 receptor, (+)SKF-10047 to determine the effect of sigma-1 receptor on Brdu (bromodeoxyuridine) labeling positive cells, migration as well as GFAP (glial fibrillary acidic protein) expression of astrocyte. The results showed that (+)SKF-10047 notably increased the number of Brdu labeling positive cells, migration, and the expression of GFAP in primary astrocytes, which were blocked by antagonist of sigma-1 receptor. Moreover, we also found that (+)SKF-10047 increased the phosphorylation of ERK1/2 (extracellular signal-regulated kinases 1/2) and GSK3 beta (glycogen synthase kinase 3 beta) (ser 9) in the primary astrocytes. In addition, pharmacological inhibition of ERK1/2 and GSK3 beta (ser 9) abolished sigma-1 receptor-promoted activation of astrocyte. Therefore, sigma-1 receptor could be considerate as a new pattern for modulating astrocytic function might emerge as therapeutic strategies.