The prokineticin receptor antagonist PC1 rescues memory impairment induced by β amyloid administration through the modulation of prokineticin system. (1st November 2019)

• Record Type: Journal Article
• Authors: Maftei, Daniela; Ratano, Patrizia; Fusco, Ilaria; Marconi, Veronica; Squillace, Silvia; Negri, Lucia; Severini, Cinzia; Balboni, Gianfranco; Steardo, Luca; Bronzuoli, Maria Rosanna; Scuderi, Caterina; Campolongo, Patrizia; Lattanzi, Roberta
• Is Part Of: Neuropharmacology. Volume 158(2019)
• Publication Date: 2019-11-01
• Subjects: Alzheimer's disease -- Amyloid β -- Animal model -- Prokineticin 2 -- Prokineticin receptors -- Prokineticin receptor antagonist -- Neuroprotection -- Neurogenesis; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107739
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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 Aβ1-42 and behavioral responses as well as the expression profile in hippocampus of prokineticin 2 and its receptors were investigated. Results demonstrated that Aβ1–42 -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 Aβ1–42 -infused rats restoring the balance of prokineticin system. This study pointed to a neuroprotective role of PC1 on Aβ1-42 -induced memory deficits that could be ascribed to the ability of PC1 to modulate rat hippocampal prokineticin system and to recover the impaired Aβ1-42 -induced neurogenesis. This suggests that prokineticin system antagonism could be considered as a new approach for the study of AD etiopathology. Highlights: Intracerebroventricolar infusion of Aβ1-42 modulates prokineticin system in rats. PC1 improves learning capability of Aβ1–42 -infused rats decreasing PROK2 levels. PC1 restores the impaired Aβ1-42 -induced neurogenesis in hippocampus. PC1 decreases iNOS and NF-κB overexpression reducing Aβ1-42 -induced gliosis.