Xapelli S, Silva A P, Ferreira R, Malva J O
Center for Neuroscience and Cell Biology of Coimbra, 3004-517 Coimbra, Portugal.
Peptides. 2007 Feb;28(2):288-94. doi: 10.1016/j.peptides.2006.09.031. Epub 2007 Jan 8.
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 12muM kainate (KA) for 24h 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 Y(1) or Y(2) receptors 30min 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 Y(1) or Y(2) receptors antagonists, BIBP3226 (1muM) or BIIE0246 (1muM), resulted in the loss of the neuroprotection induced by the activation of Y(1) or Y(2) receptors, respectively, in all hippocampal subfields. Taken together these results suggest that activation of NPY Y(1) or Y(2) receptors activates neuroprotective pathways that are able to rescue neurons from excitotoxic cell death.
在本研究中，我们调查了神经肽Y（NPY）在大鼠海马脑片培养物兴奋性毒性损伤后的神经保护作用。将2周龄大鼠海马脑片培养物暴露于12μM海藻酸（KA）24小时，可诱导齿状回（DG）颗粒细胞层、CA1和CA3锥体细胞层的神经元死亡，这可通过细胞碘化丙啶（PI）摄取来定量。在用海藻酸开始暴露于兴奋性毒性损伤30分钟后激活Y（1）或Y（2）受体，可通过减少DG、CA1和CA3细胞层中的PI摄取而产生神经保护作用。使用Y（1）或Y（2）受体拮抗剂BIBP3226（1μM）或BIIE0246（1μM），分别导致在所有海马亚区中Y（1）或Y（2）受体激活所诱导的神经保护作用丧失。综上所述，这些结果表明，NPY Y（1）或Y（2）受体的激活可激活能够使神经元从兴奋性毒性细胞死亡中获救的神经保护途径。
