Neuropeptide Y can rescue neurons from cell death following the application of an excitotoxic insult with kainate in rat organotypic hippocampal slice cultures

In the present work we investigated the neuroprotective role of neuropeptide Y (NPY) after an excitotoxic insult in rat organotypic hippocampal slice cultures. Exposure of 2 week-old rat hippocampal slice cultures to 12 μM kainate (KA) for 24 h induced neuronal death in dentate gyrus (DG) granular cell layer, CA1 and CA3 pyramidal cell layers, as quantified by cellular propidium iodide (PI) uptake. The activation of Y1 or Y2 receptors 30 min after starting the exposure to the excitotoxic insult with kainate resulted in neuroprotection by reducing the PI uptake in DG, CA1 and CA3 cell layers. The use of Y1 or Y2 receptors antagonists, BIBP3226 (1 μM) or BIIE0246 (1 μM), resulted in the loss of the neuroprotection induced by the activation of Y1 or Y2 receptors, respectively, in all hippocampal subfields. Taken together these results suggest that activation of NPY Y1 or Y2 receptors activates neuroprotective pathways that are able to rescue neurons from excitotoxic cell death.