Kovács-Valasek Andrea, Szabadfi Krisztina, Dénes Viktória, Szalontai Bálint, Tamás Andrea, Kiss Péter, Szabó Aliz, Setalo Gyorgy, Reglődi Dóra, Gábriel Robert
Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary; Department of János Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
Neuroscience. 2017 Apr 21;348:1-10. doi: 10.1016/j.neuroscience.2017.02.003. Epub 2017 Feb 13.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Cα for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Müller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system.
垂体腺苷酸环化酶激活多肽（PACAP）是一种神经营养和神经保护肽。PACAP及其受体广泛分布于视网膜中。许多报告提供了证据表明PACAP在视网膜变性中具有神经保护作用。当前的研究比较了野生型（WT）小鼠和缺乏内源性PACAP产生的基因敲除（KO）小鼠在衰老过程中，年轻（3 - 4个月）和成年（14 - 16个月）时视网膜细胞类型特异性的差异。进行了组织学、免疫细胞化学和蛋白质印迹检查。与年轻成年WT视网膜相比，年轻成年PACAP KO视网膜的标准神经化学标志物（多巴胺能细胞的酪氨酸羟化酶、水平细胞的28 kDa钙结合蛋白、视杆双极细胞的蛋白激酶Cα）染色除了特异性PACAP受体（PAC1 - R）染色外，没有显示出实质性改变。在年轻成年PACAP KO动物的双极细胞和水平细胞中，我们未检测到PAC1 - R免疫反应性。仅在PACAP KO小鼠中观察到了一些其他与年龄相关的变化。这些改变包括水平细胞和视杆双极细胞的树突向光感受器层发芽以及神经节细胞数量减少。此外，与衰老的WT视网膜相比，Müller胶质细胞显示出GFAP表达升高。此外，蛋白质印迹分析揭示了KO小鼠中ERK1/2和JNK磷酸化状态之间的显著差异，表明丝裂原活化蛋白激酶（MAPK）信号通路发生了改变。这些结果支持内源性PACAP有助于预防神经系统衰老的结论。
