PGE2-EP3 signaling pathway contributes to protective effects of misoprostol on cerebral injury in APP/PS1 mice

Tian, Xia; Ji, Chaonan; Luo, Ying; Yang, Yang; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Yang, Junqing

doi:10.18632/oncotarget.8284

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Therefore, oxidative injury represents a potential target of AD therapy. In the present study, 8-monthold APP/PS1 mice showed significant oxidative damage, as evidenced by the increased MDA content and inhibition of the antioxidant enzymes CAT and SOD, consistent with the findings reported by Tian et al and Wang et al [33,34]. However, the silibinin treatment significantly attenuated oxidative damage in APP/PS1 mice.…”

Section: Discussionsupporting

confidence: 93%

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

Bai¹,

Jin

Zhang

et al. 2019

J Physiol Sci

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Silibinin has been shown to attenuate cognitive dysfunction and inhibit amyloid-beta (Aβ) aggregation in Alzheimer's disease (AD) models. However, the underlying mechanism by which silibinin improves cognition remains poorly understood. In this study, we investigated the effect of silibinin on β-secretase levels, Aβ enzymatic degradation, and oxidative stress in the brains of APP/PS1 mice with cognitive impairments. Oral administration of silibinin for 2 months significantly attenuated the cognitive deficits of APP/PS1 mice in the Y-maze test, novel object recognition test, and Morris water maze test. Biochemical analyses revealed that silibinin decreased Aβ deposition and the levels of soluble Aβ1-40/1-42 in the hippocampus by downregulating APP and BACE1 and upregulating NEP in APP/PS1 mice. In addition, silibinin decreased the MDA content and increased the activities of the antioxidant enzymes CAT, SOD, and NO. Based on our findings, silibinin is a potentially promising agent for preventing AD-associated Aβ pathology.

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Section: Discussionsupporting

confidence: 93%

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

Bai¹,

Jin

Zhang

et al. 2019

J Physiol Sci

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“…Morris water maze was used to evaluate spatial learning and memory function of rat in each group (Kemppainen et al, 2014; Tian et al, 2016). Rats were given four trials per day for four consecutive days.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat

Yang

Chen

Zhao

et al. 2019

Front. Cell. Neurosci.

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The present study was designed to observe the effect of COX2/PGD2-related autophagy on brain injury in type 2 diabetes rats. The histopathology was detected by haematoxylin–eosin staining. The learning and memory functions were evaluated by Morris water maze. The levels of insulin and PGD2 were measured by enzyme-linked immunosorbent assay. The expressions of COX2, p-AKT(S473), p-AMPK(T172), Aβ, Beclin1, LC3BII, and p62 were measured by immunohistochemistry and Western blotting. In model rats, we found that the body weight was significantly decreased, the blood glucose levels were significantly increased, the plasma insulin content was significantly decreased, the learning and memory functions were impaired and the cortex and hippocampus neurons showed significant nuclear pyknosis. The levels of COX2, p-AKT(S473), PGD2, Aβ, Beclin1 and p62 were significantly increased, whereas the expression of p-AMPK(T172) and LC3BII was significantly decreased in the cortex and hippocampus of model rats. In meloxicam-treated rats, the body weight, blood glucose and the content of plasma insulin did not significantly change, the learning and memory functions were improved and nuclear pyknosis was improved in the cortex and hippocampus neurons. The expression of p-AMPK(T172), Beclin1 and LC3BII was significantly increased, and the levels of COX2, p-AKT(S473), PGD2, Aβ, and p62 were significantly decreased in the cortex and hippocampus of meloxicam-treated rats. Our results suggested that the inhibition of COX2/PGD2-related autophagy was involved in the mechanism of brain injury caused by type 2 diabetes in rats.

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“…At week 18, a Morris water maze test was performed in all rats as previously described. 28 The temperature of the water was maintained between 20 and 25 °C. The test program included two stages, with the first stage being the navigation training, which lasted for 4 days.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…At week 18, a Morris water maze test was performed in all rats as previously described . The temperature of the water was maintained between 20 and 25 °C.…”

Section: Materials and Methodsmentioning

confidence: 99%

Meloxicam Improves Cognitive Impairment of Diabetic Rats through COX2-PGE2-EPs-cAMP/pPKA Pathway

Luo

et al. 2018

Mol. Pharmaceutics

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Diabetics often face greater risk of cognitive impairment than nondiabetics. However, how to prevent this disease is still unconfirmed. In this study, we investigated the potential protection and mechanism of meloxicam on cognitive impairment in diabetic rats. The diabetic rat model was established with a high-fat diet and a small dose of streptozotocin (40 mg/kg). The changes of spatial learning and memory, histopathology, and the protein expressions of amyloid protein precursor (APP) and β-amyloid (Aβ) indicated that diabetic rats had neuronal injury and cognitive impairment. Tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C reactive protein (CRP) and prostaglandin E2 (PGE2) levels, and microglial cell number were significantly increased in the diabetic rat brain. Meanwhile, the protein expressions of APP, Aβ, cyclooxygenases2 (COX2), E-type prostanoid recptors 1 (EP1) and EP2, and the level of cyclic adenosine monophosphate (cAMP) were significantly increased, while the protein expressions of EP3 and phosphorylated protein kinase A (pPKA) were significantly decreased in the diabetic rat hippocampus and cortex. However, the EP4 protein expression had no significant changes. Meloxicam significantly improved neuronal injury and cognitive impairment, and significantly decreased inflammatory cytokines levels. Meloxicam also significantly decreased the protein expressions of APP, Aβ, COX2, EP1 and EP2, and the level of cAMP and significantly increased the EP3 and pPKA protein expressions in rat hippocampus and cortex. However, meloxicam did not significantly influence the levels of blood glucose, lipids, and insulin of rats. Our results suggest that meloxicam could significantly protect diabetic rats from cognitive impairment via a mechanism that may be associated with rebalancing the COX2-PGE2-EPs-cAMP/PKA pathway.

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PGE2-EP3 signaling pathway contributes to protective effects of misoprostol on cerebral injury in APP/PS1 mice

Cited by 8 publications

References 33 publications

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat

Meloxicam Improves Cognitive Impairment of Diabetic Rats through COX2-PGE2-EPs-cAMP/pPKA Pathway

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