Depolarization promotes survival of ciliary ganglion neurons by BDNF-dependent and -independent mechanisms.
Depolarization promotes survival of ciliary ganglion neurons by BDNF-dependent and -independent mechanisms.
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去极化通过 BDNF 依赖性和非依赖性机制促进睫状神经节神经元的存活。
DOI：
10.1016/j.ydbio.2005.12.008
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发表时间：
2006
影响因子：
2.7
通讯作者：
Margiotta,JosephF
中科院分区：
文献类型：
--
作者：
Pugh,PhyllisC;Zhou,Xiangdong;Jayakar,SelwynS;Margiotta,JosephF
膜活性上调脑源性神经营养因子（BDNF）的表达，在许多系统中协调支持神经元存活。在副交感睫状体神经节（CG）神经元中，KCl去极化模拟的活动提供了几乎完全的营养支持。虽然BDNF一直被认为不能影响CG神经元的存活，但我们现在记录了它在CG发育过程中的表达，并表明低浓度的BDNF确实通过高亲和力的TrkB受体支持存活。此外，KCl去极化增加了CG神经元培养中BDNF mRNA和蛋白的表达，并增加了BDNF的释放，证明了BDNF对活动诱导的营养支持的贡献。应用抗BDNF阻断抗体或丝裂原活化蛋白激酶（MAPK）激酶抑制剂，减弱去极化支持存活，暗示典型BDNF/TrkB信号。Ca2+-钙调蛋白激酶II （CaMKII）也是必需的，因为它与抗bdnf或MAPK激酶抑制剂联合抑制可消除或大大降低去极化的营养效应。因此，膜活性可能通过刺激BDNF的释放（BDNF结合高亲和力TrkB受体激活MAPK）和招募CaMKII来支持CG神经元的存活。随着神经节传导和BDNF比其他生长因子的有效性都增加，这种机制可能在体内发育后期具有相关性。
Membrane activity upregulates brain derived neurotrophic factor (BDNF) expression to coordinately support neuronal survival in many systems. In parasympathetic ciliary ganglion (CG) neurons, activity mimicked by KCl depolarization provides nearly full trophic support. While BDNF has been considered unable to influence CG neuronal survival, we now document its expression during CG development and show that low concentrations do support survival via high-affinity TrkB receptors. Furthermore, a contribution of BDNF to activity-induced trophic support was demonstrated by showing that KCl depolarization increased BDNF mRNA and protein in, and release of BDNF from, CG neuron cultures. Application of anti-BDNF blocking antibody or mitogen activated protein kinase (MAPK) kinase inhibitor, attenuated depolarization-supported survival, implicating canonical BDNF/TrkB signaling. Ca2+-Calmodulin kinase II (CaMKII) was also required since its inhibition combined with anti-BDNF or MAPK kinase inhibitor abolished or greatly reduced the trophic effects of depolarization. Membrane activity may thus support CG neuronal survival both by stimulating release of BDNF that binds high-affinity TrkB receptors to activate MAPK and by recruiting CaMKII. This mechanism could have relevance late in development in vivo as ganglionic transmission and the effectiveness of BDNF over other growth factors both increase.