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Int Immunopharmacol ; 84: 106546, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32413735

RESUMO

Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.


Assuntos
Apelina/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Apelina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Necroptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Serina-Treonina Quinases/imunologia , Ratos Wistar , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Estreptozocina , Fator de Necrose Tumoral alfa/imunologia
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