Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat

Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat
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DOI:
10.1016/j.neuropharm.2014.02.001
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发表时间:
2014-06-01
期刊:
影响因子:
4.7
通讯作者:
Cifuentes, Fredy
Cifuentes, Fredy
中科院分区:
医学2区
文献类型:
--
作者:
Arias, Erwin R.;Valle-Leija, Pablo;Cifuentes, Fredy

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交感神经系统的突触传递是一个受多种因素调节的可塑性过程。研究了脑源性神经营养因子(BDNF)和神经生长因子(NGF)对大鼠颈上神经节基底传递和神经节长时程增强(LTP)的影响。用40 Hz, 3 s的超最大值强电刺激交感干诱发LTP,并通过测量LTP衰减时间和LTP程度来量化LTP。神经营养因子不影响基底传递,但它们对LTP有不同的影响。BDNF (200 ng/ml)使LTP衰减时间和LTP范围延长2.0倍(p < 0.01)。NGF表现出双重作用:200 ng/ml NGF使LTP衰变时间和LIP程度分别减少到对照值的53%和32% (p < 0.0001和p < 0.02),而>350 ng/ml NGF则显著增加LTP衰变时间和LIP程度(p < 0.02)。复合动作电位的数字分析表明,神经营养因子可以改变单一动作电位的同步。在完整神经节中获得的药理学数据表明,c -2-神经酰胺使LTP增强2倍,而酪氨酸激酶活性抑制剂tyrphostin AG879逆转了NGF的阻断,并使LTP增强。在切片的神经节中,我们观察到抗trka抗体逆转了ngf诱导的LTP阻断。免疫组化研究显示,83%的神经节神经元表达TrkA, 52%表达p75受体,18%表达TrkB受体。我们认为p75神经营养因子受体和TrkB信号可能会增强LTP,而TrkA信号则会降低LTP。(C) 2014 Elsevier Ltd.版权所有。
Synaptic transmission in the sympathetic nervous system is a plastic process modulated by different factors. We characterized the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on basal transmission and ganglionic long-term potentiation (LTP) in the rat superior cervical ganglion. LTP was elicited by supramaximal tetanic stimulation (40 Hz, 3 s) of the sympathetic trunk and was quantified by measuring LTP decay time and LTP extent. Neurotrophins did not affect basal transmission, however, they differentially affected LTP. BDNF (200 ng/ml) increased LTP decay time and LTP extent 2.0-fold (p < 0.01). In contrast, NGF showed a dual effect: 200 ng/ml NGF reduced LTP decay time and LIP extent to 53% and to 32% of control value (p < 0.0001 and p < 0.02; respectively), whereas >350 ng/ml NGF significantly increased LTP decay time and LIP extent (p < 0.02). Digital analysis of compound action potentials suggests that neurotrophins could change the synchronization of unitary action potentials. Pharmacological data obtained in intact ganglia show that C-2-ceramide produced a 2-fold enhancement in LTP, whereas tyrphostin AG879, an inhibitor of tyrosine kinase activity, reversed the NGF blockade and produced by itself an enhancement in LTP. In sliced ganglia we observed that an anti-TrkA antibody reversed the NGF-induced LTP blockade. Immunohistochemistry studies revealed that 83% of ganglionic neurons express TrkA, whereas 52% express p75 receptor, and 18% express TrkB receptor. We propose that p75 neurotrophin receptors and probably TrkB signaling enhance LTP, whereas TrkA signaling reduces it. (C) 2014 Elsevier Ltd. All rights reserved.