Molecular and Cellular Neuroscience | 2019
Taxifolin protects neurons against ischemic injury in vitro via the activation of antioxidant systems and signal transduction pathways of GABAergic neurons
Abstract
&NA; Cerebral blood flow disturbances lead to the massive death of brain cells. The death of >80% of cells is observed in hippocampal cell cultures after 40 min of oxygen and glucose deprivation (ischemia‐like conditions, OGD). However, there are some populations of GABAergic neurons which are characterized by increased vulnerability to oxygen‐glucose deprivation conditions. Using fluorescent microscopy, immunocytochemical assay, vitality tests and PCR‐analysis, we have shown that population of GABAergic neurons are characterized by a different (faster) Ca2+ dynamics in response to OGD and increased basal ROS production under OGD conditions. A plant flavonoid taxifolin inhibited an excessive ROS production and an irreversible cytosolic Ca2+ concentration increase in GABAergic neurons, preventing the death of these neurons and further excitation of a neuronal network; neuroprotective effect of taxifolin increased after incubation of 24 h and correlated with increased expression of antiapoptocic and antioxidant genes Stat3 Nrf‐2 Bcl‐2, Bcl‐xL, Ikk2, and genes coding for AMPA and kainate receptor subunits; in addition, taxifolin decreased expression of prooxidant enzyme NOS and proinflammatory cytokine IL‐1&bgr;. HighlightsTaxifolin inhibits excessive ROS production in GABAergic neurons;The irreversible increase of cytosolic Ca2+ concentration in GABAergic neurons is substantially suppressed by taxifolin;Taxifolin changes expression of the pro‐ and antiapoptotic genes and the genes coding AMPA and kainate receptor subunits;Taxifolin increases survival of hippocampal cells after OGD.