Caspase-3 Activity and Autophagy Intensity in the Development of Neuronal Resistance to Glutamate Toxicity

Two periods of autophagy activation with a different significance for the development of resistance were demonstrated in the model of neuronal resistance to the toxic glutamate challenge (trophic factor deprivation). The autophagy inhibitor 3-methyladenine (3-MA) at a concentration of 1.25 mM significantly suppressed resistance development but only if applied immediately after deprivation of trophic factors. Inhibition of autophagy with 3-MA during deprivation did not affect resistance production. In addition, activation of autophagy caused a decrease in caspase-3 activity, although the mechanism of this process remains unclear. We hypothesize that development of resistance in neurons is mediated by a decrease in caspase-3 activity caused by autophagy activation.