The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons
The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons
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DOI：
10.1016/j.neulet.2006.01.046
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发表时间：
2006-05-15
影响因子：
2.5
通讯作者：
Anand, P.
中科院分区：
文献类型：
--
作者：
Anand, U.;Otto, W. R.;Anand, P.
我们在体外研究了关键神经营养因子 (NTF) 对成人感觉神经元形态、香草酸受体 1 (TRPV1) 水平以及对辣椒素反应的影响。将撕脱的背根神经节（DRG，n = 5）在联合或不联合神经生长因子（NGF）、胶质细胞（系）衍生生长因子（GDNF）和神经营养蛋白3（NT3）的情况下培养5天。在没有 NTF 的情况下，神经元的直径范围为 20 至 100 μm（平均 42 +/- 4 μm）。添加 NTF 导致神经元大小显着增加，高达 120 μm（平均直径 62 +/- 5 μm，P < 0.0 1，t 检验），TRPV1 阳性神经元总体增加 35% (P < 0.003)，特别是大的 TRPV1 阳性神经元 > 80 μm (P < 0.05)。钙比例测定法显着增强了对辣椒素的反应（P < 0.000 1）。将分离的感觉神经元短时间（1小时）暴露于NTF会增加TRPV1阳性神经元的数量，但不会增加TRPV3、Nav 1.8和IK1的数量，并且形态大小分布仍然与完整的死后DRG神经元相似。因此，NTF 在培养的人类 DRG 神经元中增加了大小，提高了 TRPV1 水平并增强了辣椒素反应；这些变化可能与疾病状态的病理生理学有关，并为研究新型镇痛药提供体外模型。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
We have studied the effect of key neurotrophic factors (NTFs) on morphology, levels of the vanilloid receptor-1 (TRPV1) and responses to capsaicin in adult human sensory neurons in vitro. Avulsed dorsal root ganglia (DRG, n = 5) were cultured with or without a combination of nerve growth factor (NGF), glial cell (line)-derived growth factor (GDNF) and neurotrophin3 (NT3) for 5 days. In the absence of NTFs, the diameter of neurons ranged from 20 to 100 mu m (mean 42 +/- 4 mu m). Adding NTFs caused a significant increase in neuronal sizes, up to 120 mu m (mean diameter 62 +/- 5 mu m, P < 0.0 1, t-test), an overall 35% increase of TRPV1-positive neurons (P < 0.003), and notably of large TRPV1 -positive neurons > 80 mu m (P < 0.05). Responses to capsaicin were significantly enhanced with calcium ratiometry (P < 0.000 1). Short duration (1h) exposure of dissociated sensory neurons to NTFs increased numbers of TRPV1 -positive neurons, but not of TRPV3, Nav 1.8 and IK1 and the morphological size-distribution remained similar to intact post-mortem DRG neurons. NTFs thus increase size, elevate TRPV1 levels and enhance capsaicin responses in cultured human DRG neurons; these changes may relate to pathophysiology in disease states, and provide an in vitro model to study novel analgesics. (c) 2006 Elsevier Ireland Ltd. All rights reserved.