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

França, Maria Eduarda Rocha de; Ramos, Renata Kelly Luna Gomes; Oliveira, W.; Duarte-Silva, Eduardo; Araújo, Shyrlene Meyre Rocha; Lós, Deniele Bezerra; Peixoto, Christina Alves

doi:10.1016/j.taap.2019.114673

Cited by 25 publications

(11 citation statements)

References 76 publications

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“…The results of a study demonstrated that treatment with tadalafil reduces neuroinflammation and neurodegeneration levels by decreasing inflammatory markers and glial activation in the cortex and hippocampus. Besides, Tadalafil also promoted synaptic plasticity by increasing PKA/PKG/CREB/BDNF/NeuN/synaptophysin, normalized the expression of hippocampal glutamate receptors, and restored spatial learning ability and memory [62].…”

Section: Discussionmentioning

confidence: 92%

Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

et al. 2021

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Accumulated evidence shows that the cAMP and cGMP signaling pathway plays an important role in memory function and neuronal plasticity. Phosphodiesterase 5 (PDE5) is a hopeful therapeutic target in AD (Alzheimer disease), and PDE5 inhibition may be a good therapeutic strategy for the treatment of AD. In the present study, the four-day bilateral intra-hippocampal infusion of H-89 as a protein kinase AII inhibitor (10 µM/side) and intra-peritoneal injections of tadalafil (20 mg/kg) and scopolamine (0.5 mg/kg) alone and also on combination on spatial learning in Morris water maze (MWM) were investigated. DMSO and saline were used as controls for H-89 and other mentioned drugs, respectively. Rats were trained for 4 days; each day included one block of four trials. Post- training probe trial tests were performed on day 5. Administration of H-89 and scopolamine led to a significant impairment in spatial learning compared to their related controls. But, combination of tadalafil/H-89 or tadalafil/scopolamine reversed H-89 or scopolamine- induced spatial learning deficits in MWM. Taken together, these results showed the probable regulatory effects of cGMP on cholinergic and cAMP/PKA signaling pathways in co-administrations of these mentioned drugs on spatial learning in MWM.

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Section: Discussionmentioning

confidence: 92%

Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

et al. 2021

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“…However, this increase in the serum TNF-α and IL-6 level was significantly blocked by Tadalafil treatment when compared to the corresponding irradiated rats group. Suppression of serum TNF-α and IL-6 levels clearly indicates the anti-inflammatory effect of Tadalafil (França et al, 2019). Also, Wang et al (2020) concluded that after irradiation, inflammatory reactions are developed in the organisms and they supposed that inflammation arises from activation of TNF-α, so its inhibition can be very useful in the treatment of radiation-induced diseases.…”

Section: Discussionmentioning

confidence: 97%

Tadalafil Attenuates γ-Rays-Induced Hepatic Injury in Rats

Khouly

Ebrahim

2020

Egypt. J. Rad.Sci.

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T ADALAFIL is widely used in the treatment of many disease disorders. Tadalafil is studied for its protective effect against γ-rays-induced hepatic injury in rats. Rats were exposed to 6 Gy-γ-rays then, treated with Tadalafil for 7-days and compared to the control, Tadalafil alone and irradiated groups. Oxidative-stress markers; malondialdehyde (MAD) and myeloperoxidase (MPO) and the antioxidant markers; reduced glutathione (GSH) content, and the relative enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in liver tissues. The anti-inflammatory markers; tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated in the blood serum. Data revealed a significant reduction in the γ-rays-induced lipid-peroxidation; MDA content, MPO activity, the inflammatory markers levels of TNF-α and IL-6, and an augmentation in the antioxidant marker levels of GSH, GPx, CAT and SOD. It could be concluded that Tadalafil could alleviate the toxic effects of ionizing radiation in liver via the strong anti-oxidant and anti-inflammatory impact, thus could be useful as a radio protective agent in the radiotherapy schedule. The radio protective influence of Tadalafil could need to be explored for further organs in imminent works.

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“…The FSHR is a G protein‐coupled receptor, and the cAMP/PKA signaling pathway, the most classical pathway, was first validated, and it was seen that FSH inhibited the cAMP/PKA pathway activity, and in a study with ethanol and 11β‐HSD2, researchers confirmed that the cAMP/PKA pathway regulates EGR1 expression [ 42 ]. What’s more, it has also been demonstrated that in some tissues, the cAMP/PKA pathway changes in the opposite direction to IL‐6, meaning that inhibition of the cAMP/PKA pathway activates the expression of IL‐6 [ 43 , 44 ]. These evidences explained the specific mechanism of the elevated expression of EGR1 and IL‐6 in our experiment.…”

Section: Discussionmentioning

confidence: 99%

Follicle‐stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation

et al. 2021

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Previous studies have found follicle‐stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up‐regulated genes, such as Col12a1 and Col1a1 , and 644 down‐regulated genes, such as MGP , were screened by transcriptomics. A subset of extracellular matrix (ECM)‐related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP , the upregulation of EGR1 and Col1a1 , and the increase of IL‐6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways.

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

Cited by 25 publications

References 76 publications

Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

Tadalafil Attenuates γ-Rays-Induced Hepatic Injury in Rats

Follicle‐stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation

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