Zassler B, Dechant G, Humpel C
Laboratory of Psychiatry, University Clinic of Psychiatry, Innsbruck Medical University, Anichstr. 35, A-6020 Innsbruck, Austria.
Neuroscience. 2005;130(2):317-23. doi: 10.1016/j.neuroscience.2004.09.010.
Cholinergic neurons degenerate in Alzheimer's disease and dementia and neuroprotective substances are of high interest to counteract this cell death. The aim of the present study was to test the effect of urea and the nitric oxide synthetase inhibitor l-thiocitrulline on the survival of cholinergic neurons. Organotypic brain slices of the basal nucleus of Meynert were cultured for 2 weeks in the presence of 1-100 microM urea with or without NGF or other growth factors or with or without 1-10 microM of the NOS inhibitor L-thiocitrulline. A high number of cholinergic neurons survived in the presence of 0.1-100 ng/ml NGF. Urea or L-thiocitrulline alone did not exhibit neuroprotective activity; however, when brain slices were incubated with urea or L-thiocitrulline together with NGF there was a significant potentiating survival effect. Incubation of brain slices with NGF + urea + L-thiocitrulline did not further enhance the number of cholinergic neurons. NGF as well as urea did not stimulate expression of the enzyme choline acetyltransferase pointing to survival promoting effects. Urea did not modulate the NGF binding in PC12 cells indicating that this effect was indirect. It is concluded that urea may play a role as an indirect survival promoting molecule possibly involving the nitric oxide pathway.
胆碱能神经元在阿尔茨海默病和痴呆症中会退化，神经保护物质对于对抗这种细胞死亡具有很高的研究价值。本研究的目的是测试尿素和一氧化氮合酶抑制剂L-硫代瓜氨酸对胆碱能神经元存活的影响。将迈内特基底核的脑片在含有1-100微摩尔尿素的情况下培养2周，同时添加或不添加神经生长因子（NGF）或其他生长因子，以及添加或不添加1-10微摩尔的一氧化氮合酶抑制剂L-硫代瓜氨酸。在存在0.1-100纳克/毫升NGF的情况下，大量胆碱能神经元存活。单独的尿素或L-硫代瓜氨酸未表现出神经保护活性；然而，当脑片与尿素或L-硫代瓜氨酸以及NGF一起孵育时，存在显著的增强存活效应。用NGF + 尿素 + L-硫代瓜氨酸孵育脑片并未进一步增加胆碱能神经元的数量。NGF以及尿素均未刺激胆碱乙酰转移酶的表达，表明其具有促进存活的作用。尿素并未调节PC12细胞中NGF的结合，表明这种作用是间接的。得出的结论是，尿素可能作为一种间接的促进存活分子发挥作用，可能涉及一氧化氮途径。
