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Inhibition of PDE5 attenuates streptozotocin-induced neuroinflammation and tau hyperphosphorylation in a streptozotocin-treated rat model.
- Source :
-
Brain research [Brain Res] 2019 Nov 01; Vol. 1722, pp. 146344. Date of Electronic Publication: 2019 Jul 22. - Publication Year :
- 2019
-
Abstract
- Intracerebroventricular (icv) streptozotocin (STZ) injection decreases cerebral insulin signal pathway function and produces multiple effects that resemble the molecular, pathological, and behavioural features of Sporadic Alzheimer's disease (SAD). We previously reported that yonkenafil (yonk), the analogue of sildenafil and a novel PDE5 inhibitor exerts an anti-amyloidogenesis effect by regulating the Aβ level and inhibiting the expression of β-amyloid precursor protein in the APP/PS1 transgenic mice model. In this study, the effects of yonk on cognitive behaviors as well as the pathological features in streptozotocin-induced SAD rat model were investigated. The results demonstrated that administration of yonk at doses of 3 and 10 mg/kg for three weeks significantly improved cognitive deficits, attenuated STZ-induced neuronal death, inhibited the over-activation of microglia and astrocytes and the levels of pro-inflammatory markers, as well as decreased PDE5 protein expression in the hippocampus. Furthermore, yonk (3 mg/kg) notably prevented changes in tau hyperphosphorylation, decreased IRS-1and JNK phosphorylation and increased the GSK3β (ser9) phosphorylation induced by STZ. In summary, these data suggested that yonk significantly reversed STZ-induced memory deficits by inhibiting the over-activation of microglia and astrocytes, as well as ameliorated the levels of pro-inflammatory makers and tau hyperphosphorylation through regulating GSK3β signalling pathway.<br /> (Copyright © 2019. Published by Elsevier B.V.)
- Subjects :
- Alzheimer Disease metabolism
Animals
Disease Models, Animal
Insulin metabolism
Male
Phosphorylation
Rats, Wistar
Encephalitis chemically induced
Encephalitis metabolism
Phosphodiesterase 5 Inhibitors administration & dosage
Pyrimidinones administration & dosage
Pyrroles administration & dosage
Streptozocin administration & dosage
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1722
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 31344367
- Full Text :
- https://doi.org/10.1016/j.brainres.2019.146344