FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia

Jiang, Xin; Niu, Xiaoli; Guo, Qingjun; Dong, Yanhong; Xu, Jing; Yin, Nan; Qi, Qianqian; Jia, Yanqiu; Gao, Lei; He, Qihui; Lv, Peiyuan

doi:10.1016/j.bbr.2018.05.023

Cited by 40 publications

(25 citation statements)

References 43 publications

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“…Apoptosis plays an important role in the pathophysiological mechanisms of VD (Ye et al, 2017). In agreement with previous findings, it was found that Bcl-2/Bax ratio was decreased in the hippocampus of VD animals (Chen et al, 2018b;Jiang et al, 2019) and bpV(pis) reversed this decrease of the Bcl-2/Bax expression ratio that was induced by 2VO in VD model rats.…”

Section: Discussionsupporting

confidence: 88%

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia

Yuan,

Zhu,

Chen

et al. 2019

J. Integr. Neurosci.

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Vascular dementia is the second most common type of dementia, yet no effective treatment for it exists. Akt and Erk1/2 signaling pathways are involved in neuronal survival. It has been reported that bisperoxovanadium (pyridin-2-squaramide), a novel squaramide compound, protects against cerebral ischemia injury via activation of Akt and Erk1/2. Here, the potential neuroprotective effect of bisperoxovanadium is shown for the first time in a model of vascular dementia induced in 6-month-old male Sprague-Dawley rats by two-vessel occlusion injury applied to 6-month-old. Following this lesion, bisperoxovanadium (pyridin-2-squaramide) (1 mg/kg/day) was intragastrically administered for four successive weeks. The Morris water maze test estimated cognitive function. The morphological examination was performed by hematoxylin-eosin staining. Akt and Erk1/2 protein abundance were assessed by Western blot. Results showed that bisperoxovanadium (pyridin-2-squaramide) attenuated not only cognitive dysfunction but also alleviated histopathological changes in rats with vascular dementia. Moreover, bisperoxovanadium (pyridin-2-squaramide) ultimately reduced neuronal apoptosis represented by the Bax/Bcl-2 ratio in the CA1 (cornu ammonis 1) region of the hippocampus. Importantly, the levels of p-Akt(ser 473) and p-Erk1/2(Thr 202 /Tyr 204) were increased after treatment with bisperoxovanadium (pyridin-2-squaramide). It is concluded that the novel squaramide compound bisperoxovanadium (pyridin-2-squaramide) might be effective in the treatment of vascular dementia by activation of Akt and Erk1/2.

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Section: Discussionsupporting

confidence: 88%

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia

Yuan,

Zhu,

Chen

et al. 2019

J. Integr. Neurosci.

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“…9,10 Studies have shown that, by reducing ROS production, hydrogen (H 2 ) can effectively inhibit autophagy activity and provide protective effects against numerous diseases. 11,12 H 2 is the lightest chemical element and can easily diffuse through membranes into cytosol and organelles, exerting anti-oxidation, anti-inflammation, and anti-apoptotic effects. 13,14 Under physiological conditions, breathing low concentrations of H 2 has been proven to be relatively safe, but as it has explosive property, the use of H 2 is limited in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Studies have shown that, by reducing ROS production, hydrogen (H 2 ) can effectively inhibit autophagy activity and provide protective effects against numerous diseases. 11,12…”

Section: Introductionmentioning

confidence: 99%

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Wang

Zhang

et al. 2019

Exp Biol Med (Maywood)

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Over-activation of autophagy due to increased levels of reactive oxygen species is a key mechanism of lipopolysaccharide-induced acute lung injury. Hydrogen-rich saline, an antioxidant, has been proved to be an effective agent for the prevention of acute lung injury, but the underlying mechanism remains unclear. Here, we investigated the mechanism through which hydrogen-rich saline prevents acute lung injury by focusing on autophagy regulation. The acute lung injury model was induced using lipopolysaccharide both in vivo and in vitro. The activation of autophagy was observed by detecting the expression of autophagy-related proteins using Western blotting. Lung histopathological changes, malondialdehyde content, wet/dry ratio, inflammatory cell count, protein content in bronchoalveolar lavage fluid, and cell viability were measured to evaluate the severity of acute lung injury. Intracellular reactive oxygen species levels were detected using dihydroethidium, which is a reactive oxygen species fluorescent probe. The results showed that the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II/I (LC3II/I ratio) was obviously increased after lipopolysaccharide administration. Pretreatment with hydrogen-rich saline markedly inhibited the expression of Beclin-1 and the LC3II/I ratio; ameliorated lung histopathological changes, malondialdehyde content and wet/dry ratio; and reduced protein content and infiltration of inflammatory cells in bronchoalveolar lavage fluid. These protective effects were also observed by pretreatment with autophagy inhibitor 3-methyladenine. Similar results were found in vitro. The production of reactive oxygen species and the activation of the AMPK/mTOR pathway were notably enhanced in MLE-12 cells after lipopolysaccharide treatment, and ameliorated by the hydrogen-rich medium. The activation of AMPK induced by lipopolysaccharide was also inhibited by pretreatment with N-acetyl-L-cysteine (a reactive oxygen species scavenger). In addition, the over-activation of autophagy was also suppressed by compound C (an AMPK inhibitor). In conclusion, hydrogen-rich saline alleviated lipopolysaccharide-induced acute lung injury by inhibiting excessive autophagy activation via the ROS/AMPK/mTOR pathway in mice. Hydrogen-rich saline may be a new therapeutic strategy for acute lung injury prevention and treatment in the future. Impact statement Acute lung injury (ALI), a common complication of many serious health issues, such as serious infection, burns, and shock, is one of the most common critical illnesses in clinical practice with a high mortality rate of 30–40%. There are still short of effective prevention and treatment measures. Evidence is growing that hydrogen-rich saline (HRS) may be an effective drug for the prevention and treatment of ALI. However, the mechanisms involved in have not been clearly understood. In this study, we investigated the underling mechanisms by focusing on autophagy regulation. The results showed that HRS ameliorated lipopolysaccharide-induced ALI in mice by inhibiting autophagy over-activation through ROS/AMPK/mTOR pathway. HRS may be a new therapeutic strategy for ALI prevention and treatment in the future.

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“…Mice lacking complete circle of Willis will suffer from severe ischemia and even death if perform 2VO [23]. Recently, UCCAO model is adopted for VD mice model, which is modified from 2VO model [24]. After 28 days of permanently ligated of a common carotid artery, cerebral perfusion in the ipsilateral hemisphere of mice declined by 35-55% [25].…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin protects cognitive function of vascular dementia

et al. 2020

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Objective The purpose of this study was to evaluate the effect of astaxanthin (AST) on cognition function, inflammatory response and oxidative stress in vascular dementia (VD) mice. Method VD mice model was established by left unilateral common carotid arteries occlusion (LUCCAO). Following LUCCAO, AST was intragastrically administered for 30 days. Object recognition test and morris water maze test were used to evaluate cognitive function. Hematoxylin and eosin staining was performed to observe the hippocampal neuron structure. Enzyme-linked immunosorbent assay kit and bicinchoninic acid kit were respectively adopted to measure IL-1β and IL-4 protein expression and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus and prefrontal cortex. Results AST improved the discrimination ability of VD mice. The escape latency and path length of VD mice treated with AST were dramatically reduced. Besides, AST 200 mg/kg enhanced crossing platform time and the number of times crossing the platform quadrant, and alleviated the morphological impairment in VD mice. Moreover, we found that AST inhibited IL-1β expression and MDA content, whereas promoted IL-4 expression and SOD activity in a dose-dependent manner. Conclusion AST could improve cognitive impairment and hippocampal neurons in VD mice, which may be related to suppression of inflammatory response and oxidative stress.

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FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia

Cited by 40 publications

References 43 publications

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Astaxanthin protects cognitive function of vascular dementia

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