These data show that adding HA-M-EV to hippocampal slices from control rats enhances activation of the TNFα–TNFR1–S1PR2–IL-1β–BDNF–TrkB pathway and alters the membrane expression of NMDA and AMPA receptors in a manner similar to that observed in vivo in hyperammonemia. The gene discussed is S1PR2; the disease is Hyperammonemia.