Antonawich F J, Azmitia E C, Strand F L
Department of Biology, New York University, NY 10003.
Peptides. 1993 Nov-Dec;14(6):1317-24. doi: 10.1016/0196-9781(93)90192-j.
ACTH peptide fragments demonstrate potent neurotrophic effects on peripheral nerves in situ, central neurons in culture, and have been implicated to have effects on central neurons in vivo. Neurotoxic lesioning of the nigrostriatal system, which depletes the striatum of dopamine, provides a feasible model of central regeneration in which to test these peptides. Male Sprague-Dawley rats were lesioned unilaterally with 6-hydroxydopamine (8 micrograms/4 microliters), infused into the substantia nigra. They were subsequently treated with 10 micrograms/kg IP of Org 2766 [ACTH/MSH(4-9) analogue] or saline every 24 h starting immediately after the infusion and were observed for 2 weeks. Rotational behavior data indicate that Org 2766 significantly decreases ipsiversive turning (p < 0.05), induced by amphetamine (2 mg/kg), as well as accelerating the onset of denervation supersensitivity induced by apomorphine (0.05 mg/kg). Evaluation of dopamine immunohistochemistry, using an anti-tyrosine hydroxylase antibody, demonstrates an enhanced intensity of staining in the ORG 2766-treated tissue compared to its saline counterpart. This difference is confirmed and quantified through specific high-affinity dopamine uptake. Dopamine uptake is about 17% higher in the striata of animals treated with Org 2766. Higher dopamine uptake levels in these ACTH-treated animals correlate with greater fiber density in this group. Therefore, it appears that treatment with the ACTH/MSH(4-9) analogue Org 2766 (10 micrograms/kg/24 h) offers a protective effect from 6-OHDA lesions in the substantia nigra as well as accelerating various compensatory mechanisms involved in functional recovery.
促肾上腺皮质激素（ACTH）肽片段对原位外周神经和培养中的中枢神经元显示出强大的神经营养作用，并且被认为对体内中枢神经元也有影响。黑质纹状体系统的神经毒性损伤会使纹状体中的多巴胺耗竭，这为测试这些肽提供了一个可行的中枢再生模型。将雄性斯普拉格-道利大鼠单侧用6-羟基多巴胺（8微克/4微升）注入黑质进行损伤。在注入后立即开始，每24小时给它们腹腔注射10微克/千克的Org 2766[促肾上腺皮质激素/促黑素（4-9）类似物]或生理盐水，并观察2周。旋转行为数据表明，Org 2766显著减少了由苯丙胺（2毫克/千克）诱导的同侧旋转（p<0.05），并加速了由阿扑吗啡（0.05毫克/千克）诱导的去神经超敏反应的发生。使用抗酪氨酸羟化酶抗体对多巴胺免疫组织化学进行评估，结果显示与生理盐水处理的组织相比，Org 2766处理的组织中染色强度增强。通过特异性高亲和力多巴胺摄取来证实和量化这种差异。在接受Org 2766处理的动物的纹状体中，多巴胺摄取约高17%。这些接受促肾上腺皮质激素处理的动物中较高的多巴胺摄取水平与该组中更大的纤维密度相关。因此，似乎用促肾上腺皮质激素/促黑素（4-9）类似物Org 2766（10微克/千克/24小时）进行处理可对黑质中的6-OHDA损伤起到保护作用，并加速参与功能恢复的各种代偿机制。
