Laboratory of Cellular & Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Sydney, NSW 2007, Australia.
Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2024 Aug 14;25(16):8850. doi: 10.3390/ijms25168850.
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing-remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors' levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and/or other demyelinating disorders.
垂体腺苷酸环化酶激活肽 (PACAP) 和血管活性肠肽 (VIP) 是中枢神经系统 (CNS) 中的两种神经保护和抗炎分子。两者都与三种 G 蛋白偶联受体结合，即 PAC1、VPAC1 和 VPAC2，以在各种 CNS 疾病中发挥其有益作用，包括多发性硬化症 (MS)。在这项研究中，我们评估了具有复发缓解型 MS (RRMS)、原发性 MS (PPMS)、继发性进展型 MS (SPMS) 或年龄匹配的非-MS 对照临床病史的 MS 供体正常外观白质 (NAWM) 中 PACAP/VIP 受体的表达和分布。基因表达研究显示 PACAP 和 VIP 以及 NAWM 中受体水平存在 MS 亚型特异性变化，免疫组织化学分析部分证实了这一点。大多数 PAC1 免疫反应性仅限于产生髓鞘的细胞，而 VPAC1 反应性弥漫在神经胶质中，并且 VPAC2 存在于小血管壁中。在损伤区域内和周围，神经胶质细胞是表现出不同 PACAP/VIP 受体反应性的主要群体，在不同的 MS 亚型中具有不同的模式。总之，这些数据确定了 PACAP/VIP 受体在不同 MS 临床实体中的差异表达模式。这些结果可能为开发针对 MS 和/或其他脱髓鞘疾病的个体化治疗方法提供机会。
