Neuroprotective effects of stanniocalcin 2 following kainic acid-induced hippocampal degeneration in ICR mice

Stanniocalcin 2 (STC2), the paralog of STC1, has been shown to act as a novel target of the mammalian unfolded protein response. We investigated the potential neuroprotective actions of STC2 against kainic acid toxicity in the hippocampus of ICR mice. STC2-treated mice experienced less neuronal cell loss in the CA3 area of the hippocampus. Also, microglial activation and heme oxygenase 1 expression were attenuated in the hippocampus of STC2-treated mice. To confirm whether STC2 regulates microglial activation directly, nitric oxide levels were measured in BV2 cells cultured with and without 10 nM STC2. STC2 decreased the level of nitric oxide induced by lipopolysaccharide (LPS) treatment significantly. Also, STC2 pretreatment significantly decreased TNF-α and IL-1β expression induced by LPS treatment. These observations demonstrated that STC2 exerts neuroprotective actions against excitotoxic insults through the inhibition of microglial activation.

Research highlights▶ STC2 attenuates KA-induced neuronal death. ▶ STC2 attenuates KA-induced microglial activation. ▶ STC2 attenuates KA-induced HO-1 expression in the glial cells. ▶ STC2 inhibits expression levels of NO, TNF-α, and IL-1β in LPS-stimulated BV2 cells.