Xiong H, Yamada K, Han D, Nabeshima T, Enikolopov G, Carnahan J, Nawa H
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Eur J Neurosci. 1999 May;11(5):1567-76. doi: 10.1046/j.1460-9568.1999.00567.x.
The diffusible factors, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) are both suggested to be intercellular messengers that have similar synaptic activities and developmental influences in the brain. In the present study, we have analysed their mutual regulation with respect to their production in rodent neocortical neurons. Some of the cultured rat neocortical neurons exhibited immunoreactivity for both neuronal NO synthase (NOS) and the BDNF receptor trkB. Neuronal NOS appeared to be activated autonomously and produced NO in culture as monitored by nitrite accumulation. Inhibition of the endogenous NO production in culture by a NOS inhibitor, NG-monomethyl-L-arginine (NMMA), enhanced basal expression of BDNF mRNA and protein. Similarly, cerebroventricular administration of another NOS inhibitor, N-omega-nitro-L-arginine methylester (L-NAME), but not D-NAME or saline, increased BDNF content in the neocortex. In the opposite direction, however, BDNF appeared to function as a positive regulator for NO synthesis. Addition of BDNF upregulated the neuronal NOS expression as well as NO production in neocortical culture. In agreement, BDNF knock-out mice exhibited significant impairment of neuronal NOS expression in the neocortex. Taken together, these observations suggest that the trans-synaptic signalling molecules, NO and BDNF, influence the production of each other and mutually regulate the strength of their intercellular communications.
可扩散因子一氧化氮（NO）和脑源性神经营养因子（BDNF）均被认为是细胞间信使，在大脑中具有相似的突触活性和发育影响。在本研究中，我们分析了它们在啮齿动物新皮质神经元中产生方面的相互调节作用。一些培养的大鼠新皮质神经元对神经元型一氧化氮合酶（NOS）和BDNF受体trkB均表现出免疫反应性。通过亚硝酸盐积累监测发现，神经元型NOS似乎在培养中自主激活并产生NO。NOS抑制剂NG-单甲基-L-精氨酸（NMMA）抑制培养物中内源性NO的产生，增强了BDNF mRNA和蛋白质的基础表达。同样，脑室注射另一种NOS抑制剂N-ω-硝基-L-精氨酸甲酯（L-NAME），而不是D-NAME或生理盐水，增加了新皮质中BDNF的含量。然而，在相反的方向上，BDNF似乎作为NO合成的正调节因子发挥作用。添加BDNF上调了新皮质培养物中神经元型NOS的表达以及NO的产生。与此一致的是，BDNF基因敲除小鼠的新皮质中神经元型NOS表达明显受损。综上所述，这些观察结果表明，跨突触信号分子NO和BDNF相互影响彼此的产生，并相互调节它们细胞间通讯的强度。
