TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway

Y, Hu; Chen, Wei; Wu, Lin; Jiang, Lin; Liang, Ning; Tan, Lulu; Liang, Mengya; Tang, Nong

doi:10.1007/s12031-018-1219-7

Cited by 45 publications

(27 citation statements)

References 30 publications

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“…For instance, simulation of the PI3K/AKT/mTOR pathway could inhibit cell apoptosis to mediate the neuroprotective effect in a cellular model of PD [40]. Research also explained that the blockage of Wnt/ b-catenin pathway was partially activated to protect nerve cells in PD and AD [41,42]. The report also explicated that miRNAs protected cell from damage via regulating the above two kinds of pathways in neurodegenerative diseases [43,44].…”

Section: Discussionmentioning

confidence: 97%

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Yang

Kong

2020

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells. Methods: The PC12 cells were incubated by hydrogen peroxide (H 2 O 2) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1a expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1a was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/b-catenin pathways was tested by western blot. Results: Dex attenuated H 2 O 2-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1a expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3 0-UTR of HIF-1a. In addition, Dex activated PI3K/AKT/mTOR and Wnt/b-catenin pathways by declining miR-199a level. Conclusions: This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/ HIF-1a.

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Section: Discussionmentioning

confidence: 97%

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Yang

Kong

2020

Artificial Cells, Nanomedicine, and Biotechnology

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“…Wnt signaling is critical for the normal function of the brain, which plays a key role in both nervous system development and adult synaptic plasticity [ 9 ]. Activation of the Wnt/β-catenin pathway can improve memory function and synaptic plasticity [ 10 , 11 ]. Previous studies have shown that Pb exposure causes cognitive deficits and synaptogenesis impairments by inhibiting the canonical Wnt pathway in vivo and in vitro [ 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Pb exposure could cause oxidative stress, inflammation and apoptosis by inhibiting the activations of nuclear factor erythroid 2–related factor 2 (Nrf2) and homoxygenase-1 (HO-1) in brain of rats [ 1 , 16 ]. Prenatal Pb exposure could contribute to deficits in synaptic plasticity, which result in the amyloid-beta (Aβ) deposition, tau phosphorylation, mitochondrial dysfunction, caspase activation, and even cellular apoptosis [ 8 , 11 , 12 , 17 ]. However, to our knowledge, it has never been reported whether GAS could regulate the Wnt/Nrf2 pathway to protect the brain against Pb-induced injury.…”

Section: Introductionmentioning

confidence: 99%

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

et al. 2020

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Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

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“…Transforming growth factor-beta type I (TGF-β1) signaling pathway is also closely related to AD, especially due to its involvement in neuronal development and synaptic plasticity [47]. Accordingly, dysfunctions in TGF-β1 signaling are associated with increased neurodegeneration, promoted by an increment of Aβ deposition and neurofibrillary tangle formation [48,49]. These altogether suggest that, by altering the expression of miRNAs that regulate important pathways associated with AD, OSA may indirectly affect the progression of AD.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA Profile Associated with Obstructive Sleep Apnea in Alzheimer’s Disease

et al. 2020

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The diagnosis of obstructive sleep apnea (OSA) in Alzheimer's disease (AD) by polysomnography (PSG) is challenging due to the required collaboration of the patients. In addition, screening questionnaires have demonstrated limited usefulness with this subpopulation. Considering this, we investigated the circulating microRNA (miRNA) profile associated with OSA in AD patients. This study included a carefully selected cohort of females with mild-moderate AD confirmed by biological evaluation (n = 29). The individuals were submitted to one-night PSG to diagnose OSA (apnea-hypopnea index ≥ 15/h) and the blood was collected in the following morning. The plasma miRNA profile was evaluated using RT-qPCR. The patients had a mean (SD) age of 75.8 (5.99) years old with a body mass index of 28.6 (3.83) kg m −2. We observed a subset of 15 miRNAs differentially expressed between OSA and non-OSA patients, of which 10 were significantly correlated with the severity of OSA. Based on this, we built a prediction model that generated an AUC (95% CI) of 0.95 (0.88-1.00) including 5 of the differentially expressed miRNAs that correlated with OSA severity: miR-26a-5p, miR-30a-3p, miR-374a-5p, miR-377-3p, and miR-545-3p. Our preliminary results suggest a plasma miRNA signature associated with the presence of OSA in AD patients. Further studies will be necessary to validate these findings.

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TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway

Cited by 45 publications

References 30 publications

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Circulating MicroRNA Profile Associated with Obstructive Sleep Apnea in Alzheimer’s Disease

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