Tadalafil restores long-term memory and synaptic plasticity in mice with hepatic encephalopathy.
Toxicol Appl Pharmacol
; 379: 114673, 2019 09 15.
Article
em En
| MEDLINE
| ID: mdl-31323263
BACKGROUND AND AIM: Tadalafil displays important neuroprotective effects in experimental models of neurodegenerative diseases, however its mechanisms of action remain poorly understood. The aim of the present study was to investigate the action of Tadalafil on learning and memory, neuroinflammation, glial cell activation and neuroprotection in the experimental model of hepatic encephalopathy (HE) induced by Thioacetamide (TAA) in mice. METHODS: Mice received intraperitoneal injections of TAA, for 3 consecutive days, reaching the final dose of 600â¯mg/kg. Tadalafil 15â¯mg/kg body weight was administered by gavage during 15â¯days after TAA induction. Mice underwent a Barnes maze for learning and memory evaluation. RESULTS: Animals with hepatic encephalopathy showed reduced learning and spatial memory in the Barnes Maze, presented astrocyte and microglia activation and increased neuroinflammatory markers such as TNF-α, IL-1ß, IL-6, p-p38, p-ERK and p-NF-kB. In addition, the signaling pathway PKA/PKG/CREB/BDNF/NeuN/synaptophysin and glutamate receptors were deregulated by TAA. Tadalafil treatment regulated the inflammation signaling pathways restoring learning and spatial memory. CONCLUSION: Tadalafil significantly reduced neuroinflammation, promoted neuroprotection and plasticity, regulated the expression of hippocampal glutamate receptor and restored spatial learning ability and memory.
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1
Base de dados:
MEDLINE
Assunto principal:
Encefalopatia Hepática
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Fármacos Neuroprotetores
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Memória de Longo Prazo
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Tadalafila
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Transtornos da Memória
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Plasticidade Neuronal
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article