Tadalafil restores long-term memory and synaptic plasticity in mice with hepatic encephalopathy.

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 600 mg/kg. Tadalafil 15 mg/kg body weight was administered by gavage during 15 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-1β, 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.