Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons

Introduction: Tumor necrosis factor alpha (TNF?) plays a physiological role in controlling synaptic transmission and plasticity in the healthy central nervous system by modulating glutamate receptor trafficking to the plasma membrane. TNF? expression is also rapidly induced in response to tissue injury and infection. By promoting the insertion of Ca²⁺ permeable-AMPA receptors into the neuronal plasma membrane, this cytokine may cause excessive Ca²⁺ influx into neurons, thus enhancing neuronal death. Methods: Primary cultures of cortical neurons were obtained from E18 foetal mice and incubated for 24 h with adult neural stem cells (aNPCs) either stimulated with lipopolysaccharide (LPS⁺aNPCs) or not (aNPCs). Cultures were treated with TNF? (100 ng/ml), and electrophysiological recordings were performed in different conditions to evaluate the effect of the cytokine on neuronal transmission. Results: In this study, we demonstrate that aNPCs from the subventricular zone reverse the effects induced by the cytokine. Moreover, we show that the effect of aNPCs on cortical neurons is mediated by cannabinoid CB1 receptor activation. Conclusion: These data suggest that the role of aNPCs in preventing excitatory neurotransmission potentiation induced by TNF? on cortical neurons may have important implications for pathologies characterized by an inflammatory component affecting cortical neurons such as Alzheimer's disease.