The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase-activating peptide promote axonal sprouting of primary afferent and cranial motor neurones
The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase-activating peptide promote axonal sprouting of primary afferent and cranial motor neurones
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DOI：
10.1111/j.1460-9568.2006.05029.x
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Klimaschewski, Lars
中科院分区：
文献类型：
--
作者：
Suarez, Victor;Guntinas-Lichius, Orlando;Klimaschewski, Lars
神经肽甘丙肽和垂体腺苷酸环化酶激活肽（PACAP）在周围神经损伤后表达显著上调。这两种肽都参与发育过程中的神经元分化和神经突生长。在这项研究中，我们研究了甘丙肽和PACAP对成年大鼠体外感觉神经元和体内面运动神经元轴突伸长和发芽的影响。将分离的大鼠背根神经节神经元铺在层粘连蛋白基底上并进行形态计量学分析。甘丙肽或PACAP（2-5 μ M）的存在下，平均轴突长度和分支点的数量显着增加。在大鼠面神经损伤模型中，通过将肽直接应用于使横断的面神经残端成管的胶原填充的导管来研究对轴突侧支化的影响。脑干神经元的三重逆行标记证实，这些肽有效地诱导颅运动神经元的轴突发芽。再生成确定的支的面神经的神经元的数量增加了五倍。搅拌行为的生物统计学分析表明，甘丙肽和PACAP损害的功能结果相比，车辆治疗的动物手术后8周。总之，虽然甘丙肽和PACAP已被确定为神经营养分子轴突的发育和再生，其作为治疗周围神经病变的潜力似乎有限，因为侧支轴突分支的广泛刺激。这些分支被错误地引向不正确的肌肉，并导致其协调活动受损。
The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2-5 mu M). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen-filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle-treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.