Takei N, Skoglösa Y, Lindholm D
Department of Neuroscience, Uppsala University, Sweden.
J Neurosci Res. 1998 Dec 1;54(5):698-706. doi: 10.1002/(SICI)1097-4547(19981201)54:5<698::AID-JNR15>3.0.CO;2-5.
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity.
神经肽垂体腺苷酸环化酶激活多肽（PACAP）存在于成年和发育中的大脑的许多区域，PACAP的受体也是如此。PACAP刺激神经元中的不同信号级联反应，涉及环磷酸腺苷（cAMP）、丝裂原活化蛋白激酶（MAP激酶）和钙。这些特性表明PACAP可能影响神经元发育。在这里，我们使用来自胚胎大鼠的原代培养物研究了PACAP对中脑多巴胺能神经元的影响。PACAP增加了酪氨酸羟化酶（TH）免疫反应性神经元的数量，提高了TH蛋白水平，并增强了这些培养物中氚标记多巴胺的摄取。此外，PACAP抵消了6-羟基多巴胺处理的影响，后者会诱导多巴胺能神经元的细胞死亡。原位杂交显示，PACAP和1型PACAP受体存在于发育中和成年大鼠的中脑中。这些结果表明，PACAP对多巴胺能神经元具有神经营养作用，并部分保护它们免受6-OHDA诱导的神经毒性。
