The prokineticin receptor antagonist PC1 rescues memory impairment induced by ß amyloid administration through the modulation of prokineticin system.
Neuropharmacology
; 158: 107739, 2019 11 01.
Article
em En
| MEDLINE
| ID: mdl-31408628
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 ß-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 Aß1-42 and behavioral responses as well as the expression profile in hippocampus of prokineticin 2 and its receptors were investigated. Results demonstrated that Aß1-42-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 Aß1-42-infused rats restoring the balance of prokineticin system. This study pointed to a neuroprotective role of PC1 on Aß1-42-induced memory deficits that could be ascribed to the ability of PC1 to modulate rat hippocampal prokineticin system and to recover the impaired Aß1-42-induced neurogenesis. This suggests that prokineticin system antagonism could be considered as a new approach for the study of AD etiopathology.
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1
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
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Receptores de Peptídeos
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Fármacos Neuroprotetores
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Receptores Acoplados a Proteínas G
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Doença de Alzheimer
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Hipocampo
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Aprendizagem
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article