Todd Keith J, Auld Daniel S, Robitaille Richard
Département de physiologie and Centre de Recherche en Sciences Neurologiques, Faculté de médecine, Université de Montréal, C.P. 6128 Succ. Centre-ville, Montréal, Québec, Canada, H3C 3J7.
Eur J Neurosci. 2007 Mar;25(5):1287-96. doi: 10.1111/j.1460-9568.2007.05385.x. Epub 2007 Mar 9.
Neurotrophins are important modulators of synaptic function at both developing and mature synapses in the CNS and PNS. At the neuromuscular junction (NMJ), neurotrophins, as well as perisynaptic Schwann cells (PSCs) are critical for the long-term maintenance and stability of the synapse. Considering this correlation and the acute interactions that occur at the synapse between PSCs and the nerve terminal, we wondered if neurotrophins could also be involved in neuron-glia signalling. To test if neurotrophins were able to signal to PSCs we used brief applications of neurotrophin-3 (NT-3), brain-derived neurotophic factor (BDNF) or nerve growth factor (NGF; 100 ng/mL). Soleus muscles of mice were incubated with the Ca(2+) indicator Fluo-4AM and Ca(2+) responses in PSCs were elicited through nerve stimulation (50 Hz, 30 s). Our results indicate that acute application of both NT-3 and BDNF, but not NGF, increased PSC Ca(2+) responses. Investigation of the mechanisms involved in these increases revealed distinct pathways for BDNF and NT-3. BDNF increased PSC responsiveness through potentiation of ATP responses while NT-3 modulated muscarinic acetylcholine receptor signalling. Using local applications of the neurotrophins, we found that both neurotrophins were able to elicit Ca(2+) responses in PSCs where BDNF used a phospholipase C-inositol 1,4,5-triphosphate (PLC-IP(3)) mechanism, while NT-3 required extracellular Ca(2+). Our results demonstrate a neurotrophin-dependent modulation of neuron-glia signalling through differential mechanisms employed by NT-3 and BDNF. Hence, neurotrophins precisely and differentially regulate PSC functions through modulation of either purinergic or cholinergic signalling pathways.
神经营养因子是中枢神经系统和周围神经系统中发育和成熟突触处突触功能的重要调节因子。在神经肌肉接头（NMJ）处，神经营养因子以及突触周围施万细胞（PSC）对于突触的长期维持和稳定性至关重要。考虑到这种相关性以及PSC与神经末梢在突触处发生的急性相互作用，我们想知道神经营养因子是否也参与神经元-胶质细胞信号传导。为了测试神经营养因子是否能够向PSC发出信号，我们短暂应用了神经营养因子-3（NT-3）、脑源性神经营养因子（BDNF）或神经生长因子（NGF；100 ng/mL）。将小鼠的比目鱼肌与Ca(2+)指示剂Fluo-4AM一起孵育，并通过神经刺激（50 Hz，30 s）引发PSC中的Ca(2+)反应。我们的结果表明，急性应用NT-3和BDNF均可增加PSC的Ca(2+)反应，但NGF则无此作用。对这些增加所涉及机制的研究揭示了BDNF和NT-3的不同途径。BDNF通过增强ATP反应来提高PSC的反应性，而NT-3则调节毒蕈碱型乙酰胆碱受体信号传导。通过局部应用神经营养因子，我们发现两种神经营养因子均能够在PSC中引发Ca(2+)反应，其中BDNF采用磷脂酶C-肌醇1,4,5-三磷酸（PLC-IP(3)）机制，而NT-3则需要细胞外Ca(2+)。我们的结果证明了神经营养因子通过NT-3和BDNF采用的不同机制对神经元-胶质细胞信号传导进行依赖性调节。因此，神经营养因子通过调节嘌呤能或胆碱能信号通路精确且差异地调节PSC功能。
