发现一种具有促神经发生和神经保护作用的化学物质。
Discovery of a proneurogenic, neuroprotective chemical.
机构信息
Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
出版信息
Cell. 2010 Jul 9;142(1):39-51. doi: 10.1016/j.cell.2010.06.018.
An in vivo screen was performed in search of chemicals capable of enhancing neuron formation in the hippocampus of adult mice. Eight of 1000 small molecules tested enhanced neuron formation in the subgranular zone of the dentate gyrus. Among these was an aminopropyl carbazole, designated P7C3, endowed with favorable pharmacological properties. In vivo studies gave evidence that P7C3 exerts its proneurogenic activity by protecting newborn neurons from apoptosis. Mice missing the gene encoding neuronal PAS domain protein 3 (NPAS3) are devoid of hippocampal neurogenesis and display malformation and electrophysiological dysfunction of the dentate gyrus. Prolonged administration of P7C3 to npas3(-/-) mice corrected these deficits by normalizing levels of apoptosis of newborn hippocampal neurons. Prolonged administration of P7C3 to aged rats also enhanced neurogenesis in the dentate gyrus, impeded neuron death, and preserved cognitive capacity as a function of terminal aging. PAPERCLIP:
进行了一项体内筛选实验，旨在寻找能够增强成年小鼠海马体神经元形成的化学物质。在测试的 1000 种小分子中，有 8 种能够增强齿状回颗粒下区的神经元形成。其中一种被称为 P7C3 的氨基丙基咔唑具有良好的药理学特性。体内研究表明，P7C3 通过保护新生神经元免于凋亡来发挥其促神经发生活性。缺失编码神经元 PAS 结构域蛋白 3（NPAS3）的基因的小鼠缺乏海马神经发生，并表现出齿状回的畸形和电生理功能障碍。将 P7C3 长期给予 npas3(-/-) 小鼠，可通过使新生海马神经元凋亡水平正常化来纠正这些缺陷。将 P7C3 长期给予老年大鼠也增强了齿状回的神经发生，阻止了神经元死亡，并保持了与终末衰老相关的认知能力。
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