Reglodi Dóra, Tamás Andrea, Lubics Andrea, Szalontay Luca, Lengvári István
Department of Anatomy, Pécs University Medical Faculty and Neurohumoral Regulations Research Group of the Hungarian Academy of Sciences, Szigeti u 12, 7624 Pécs, Hungary.
Regul Pept. 2004 Dec 15;123(1-3):85-94. doi: 10.1016/j.regpep.2004.05.016.
Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system, including neuroprotective effects. In the present study, we investigated the effects of different doses of PACAP on the functional and morphological outcome in a rat model of Parkinson's disease. Rats were given unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra. PACAP-treated animals received 1, 0.1 or 0.01 microg PACAP as a pretreatment. Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10 days post-lesion when compared to normal animals or those receiving saline only. PACAP treatment resulted in less severe acute hypokinesia, and complete recovery by 10 days. Asymmetrical signs were observed in all lesioned animals 1 day post-lesion. PACAP-treated animals, however, showed better recovery as they ceased to display asymmetrical signs 10 days later and showed markedly less apomorphine-induced rotations. Best behavioral outcome was observed in animals treated with 0.1 microg PACAP. Tyrosine-hydroxylase (TH) immunohistochemistry revealed increased number of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area in all PACAP-treated rats in contrast to the severe cell loss in control animals. These results indicate that PACAP may be a promising therapeutic agent in Parkinson's disease.
垂体腺苷酸环化酶激活多肽（PACAP）在神经系统中具有多种不同作用，包括神经保护作用。在本研究中，我们调查了不同剂量的PACAP对帕金森病大鼠模型功能和形态学结果的影响。给大鼠单侧黑质注射6-羟基多巴胺（6-OHDA）。接受PACAP治疗的动物分别接受1、0.1或0.01微克PACAP作为预处理。与正常动物或仅接受生理盐水的动物相比，未接受PACAP治疗的对照动物在损伤后1天和10天表现出严重运动迟缓。PACAP治疗导致急性运动迟缓症状较轻，并在10天时完全恢复。所有损伤动物在损伤后1天均出现不对称体征。然而，接受PACAP治疗的动物恢复情况较好，因为它们在10天后不再表现出不对称体征，且阿扑吗啡诱导的旋转明显减少。用0.1微克PACAP治疗的动物行为结果最佳。酪氨酸羟化酶（TH）免疫组织化学显示，与对照动物严重的细胞丢失相比，所有接受PACAP治疗的大鼠黑质致密部和腹侧被盖区的多巴胺能神经元数量增加。这些结果表明，PACAP可能是帕金森病一种有前景的治疗药物。
