Strand F L
Department of Biology and Center for Neural Science, New York University, New York, NY10003, USA.
Eur J Pharmacol. 2000 Sep 29;405(1-3):3-12. doi: 10.1016/s0014-2999(00)00536-7.
This review in honor of David de Wied summarizes the work done in my laboratory that first indicated that adrenocorticotropic hormone (ACTH) has a direct effect on the neuromuscular system. Cold stress or ACTH and its related peptides alpha-melanocyte-stimulating hormone (alpha-MSH ) and beta-lipotropin improve the electromechanical characteristics of adrenalectomized and hypophysectomized rats. ACTH-(1-39) accelerates the return of motor and sensory function and improves the morphological characteristics of the motor endplate after peripheral nerve crush. The non-corticotropic fragments ACTH-(4-10), alpha-MSH, the ACTH-(4-9) analogue Organon 2766 (Org 2766) or the ACTH-(4-10) analogue Biomeasure 22015 (BIM 22015) improve electrophysiological and morphological parameters of the regenerating neuromuscular system. ACTH-(4-10) immunoreactivity, present in ventral horn motor neurons in low levels, is decreased ipsilaterally following ipsilateral nerve crush but increases both ipsilaterally and contralaterally if injured animals are treated with ACTH-(4-10) indicating a neuroprotective action. Similarly, Org 2766 appears to have a protective action in the brain following nigrostriatal lesions. In developmental studies, perinatal exposure to ACTH peptides improves the structure of the neuromuscular junction, accelerates the maturation of electromechanical properties and enhances nerve-muscle integration and nerve regeneration. Perinatal exposure to these peptides decreases adult male sexual behavior, a change correlated with increased serotinergic input within the medial preoptic area. Similar changes occur in female rats and appear to be long-lasting. In tissue culture studies, both Org 2766 and BIM 22015 promote neurite outgrowth in the absence of nerve growth factor, indicating a neurotrophic role for these peptides.
这篇为纪念大卫·德·维德而作的综述总结了我实验室所开展的工作，这些工作首次表明促肾上腺皮质激素（ACTH）对神经肌肉系统具有直接作用。冷应激、ACTH及其相关肽α-黑素细胞刺激素（α-MSH）和β-促脂素可改善肾上腺切除和垂体切除大鼠的机电特性。ACTH-（1-39）可加速运动和感觉功能的恢复，并改善外周神经挤压后运动终板的形态特征。非促肾上腺皮质激素片段ACTH-（4-10）、α-MSH、ACTH-（4-9）类似物奥加农2766（Org 2766）或ACTH-（4-10）类似物生物测量22015（BIM 22015）可改善再生神经肌肉系统的电生理和形态学参数。ACTH-（4-10）免疫反应性在腹角运动神经元中含量较低，同侧神经挤压后同侧含量降低，但如果对受伤动物用ACTH-（4-10）进行治疗，则同侧和对侧含量均会增加，表明其具有神经保护作用。同样，Org 2766在黑质纹状体损伤后的大脑中似乎也具有保护作用。在发育研究中，围产期暴露于ACTH肽可改善神经肌肉接头的结构，加速机电特性的成熟，并增强神经肌肉整合和神经再生。围产期暴露于这些肽会降低成年雄性性行为，这种变化与内侧视前区内5-羟色胺能输入增加相关。雌性大鼠也会出现类似变化，且似乎具有持久性。在组织培养研究中，Org 2766和BIM 22015在无神经生长因子的情况下均可促进神经突生长，表明这些肽具有神经营养作用。
