Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy; Nanotechnology Institute, CNR-Nanotechnology Institute (CNR-NANOTEC), Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.
Neuropharmacology. 2019 Nov 1;158:107739. doi: 10.1016/j.neuropharm.2019.107739. Epub 2019 Aug 10.
Growing evidences demonstrate that chemokines and chemokine receptors are up-regulated in resident central nervous system cells during Alzheimer's disease contributing to neuroinflammation and neurodegeneration. Prokineticin 2 belongs to a new family of chemokines which recently emerged as a critical player in immune system and inflammatory diseases. Since pharmacological blockade in vitro of the prokineticin system is able to antagonize Amyloid β-induced neurotoxicity, the aim of the present study was to investigate in vivo effects of prokineticin receptor antagonist PC1 on memory impairment in a rodent model of Alzheimer's disease. Rats were intracerebroventricular infused with Aβ and behavioral responses as well as the expression profile in hippocampus of prokineticin 2 and its receptors were investigated. Results demonstrated that Aβ-infused rats developed significant memory impairments together with a marked up-regulation of both prokineticin 2 and its receptors in hippocampal neurons and astrocytes. Treatment with PC1 significantly improved learning capability of Aβ-infused rats restoring the balance of prokineticin system. This study pointed to a neuroprotective role of PC1 on Aβ-induced memory deficits that could be ascribed to the ability of PC1 to modulate rat hippocampal prokineticin system and to recover the impaired Aβ-induced neurogenesis. This suggests that prokineticin system antagonism could be considered as a new approach for the study of AD etiopathology.
越来越多的证据表明，趋化因子及其受体在阿尔茨海默病患者的中枢神经系统固有细胞中上调，导致神经炎症和神经退行性变。趋化素 2 属于趋化因子的一个新家族，最近被认为是免疫系统和炎症性疾病的关键参与者。由于体外药理学阻断促动力蛋白系统能够拮抗淀粉样β诱导的神经毒性，本研究旨在研究促动力蛋白受体拮抗剂 PC1 在阿尔茨海默病啮齿动物模型中的体内对记忆损伤的影响。用 Aβ 脑室内输注大鼠，研究其行为反应以及海马中促动力蛋白 2 及其受体的表达谱。结果表明，Aβ 输注大鼠出现明显的记忆障碍，同时海马神经元和星形胶质细胞中促动力蛋白 2 及其受体的表达明显上调。PC1 治疗显著改善了 Aβ 输注大鼠的学习能力，恢复了促动力蛋白系统的平衡。这项研究表明，PC1 对 Aβ 诱导的记忆缺陷具有神经保护作用，这可能归因于 PC1 调节大鼠海马促动力蛋白系统和恢复受损的 Aβ 诱导神经发生的能力。这表明，趋化素系统拮抗作用可能被认为是研究 AD 发病机制的一种新方法。
