Howell Owain W, Doyle Kharen, Goodman Jeffrey H, Scharfman Helen E, Herzog Herbert, Pringle Ashley, Beck-Sickinger Annette G, Gray William P
Division of Clinical Neurosciences, University of Southampton, Southampton, UK.
J Neurochem. 2005 May;93(3):560-70. doi: 10.1111/j.1471-4159.2005.03057.x.
Adult dentate neurogenesis is important for certain types of hippocampal-dependent learning and also appears to be important for the maintenance of normal mood and the behavioural effects of antidepressants. Neuropeptide Y (NPY), a peptide neurotransmitter released by interneurons in the dentate gyrus, has important effects on mood, anxiety-related behaviour and learning and memory. We report that adult NPY receptor knock-out mice have significantly reduced cell proliferation and significantly fewer immature doublecortin-positive neurons in the dentate gyrus. We also show that the neuroproliferative effect of NPY is dentate specific, is Y1-receptor mediated and involves extracellular signal-regulated kinase (ERK)1/2 activation. NPY did not exhibit any effect on cell survival in vitro but constitutive loss of the Y1 receptor in vivo resulted in greater survival of newly generated neurons and an unchanged total number of dentate granule cells. These results show that NPY stimulates neuronal precursor proliferation in the dentate gyrus and suggest that NPY-releasing interneurons may modulate dentate neurogenesis.
成年齿状回神经发生对于某些类型的海马体依赖性学习很重要，而且似乎对于维持正常情绪以及抗抑郁药的行为效应也很重要。神经肽Y（NPY）是一种由齿状回中间神经元释放的肽类神经递质，对情绪、焦虑相关行为以及学习和记忆具有重要影响。我们报告称，成年NPY受体敲除小鼠的细胞增殖显著减少，齿状回中未成熟的双皮质素阳性神经元数量也显著减少。我们还表明，NPY的神经增殖作用具有齿状回特异性，由Y1受体介导，且涉及细胞外信号调节激酶（ERK）1/2的激活。NPY在体外对细胞存活没有任何影响，但体内Y1受体的组成性缺失导致新生成神经元的存活率更高，齿状颗粒细胞总数不变。这些结果表明，NPY刺激齿状回中神经元前体细胞的增殖，并提示释放NPY的中间神经元可能调节齿状回神经发生。
