MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury

Abstract INTRODUCTION Glycine is a nonessential amino acid with known neuroprotective effects. Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite extensive research, the treatment for SAH is limited. The present study was designed to investigate the role of glycine in neuroprotection following SAH. We have previously demonstrated that glycine is involved in neuroprotection in intracerebral hemorrhage via the PTEN/AKT signal pathway. However, whether it has a role in inducing neuroprotection following SAH is not known. METHODS We established the SAH model, evaluated the SAH grade, neurological scores, brain water content, glycine-mediated C (FJC) staining, cell viability and LDH release, and did cortical neuron and microglia culture. Treatment was conducted by intracerebroventricular injection. Cultured cortical neurons and cultured cortical microglia were treated with standard ECS for 60 min and then treated with glycine (100 μM) for 60 min. Cell replacement medium was used for subsequent experiments. vPCR was performed on the Opticon 2 real-time polymerase chain reaction (PCR) detection system using the corresponding primers and SYBR gene PCR master mix. RESULTS In this present study, we show evidence of glycine mediated amelioration of neuronal death and brain edema following SAH via a novel pathway. Following SAH there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), which is reversed with glycine treatment. We also found that glycine-regulated neuroprotection following SAH via AKT activation. Glycine was shown to down-regulate PTEN by up-regulating miRNA-26b, followed by activation of AKT, resulting in inhibition of neuronal death. Inhibition of AKT, PTEN depletion or suppression of miRNA-26b blocked the neuroprotective effect of glycine. Glycine treatment also suppresses SAH-induced M1 microglial polarization and promotes anti-inflammation, which indirectly inhibits neuronal death. CONCLUSION Glycine has neuroprotective effects in SAH injury and is mediated by the miRNA-26b/PTEN/AKT signal pathway, which may be a therapeutic target for treatment of SAH injury.

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The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neurons

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666201001110937 ◽

2020 ◽

Vol 19 ◽

Author(s):

Tao Chen ◽

Li-Kun Yang ◽

Jie Zhu ◽

Chun-Hua Hang ◽

Yu-Hai Wang

Keyword(s):

Traumatic Brain Injury ◽

Protective Effect ◽

Neuronal Death ◽

Cortical Neurons ◽

Therapeutic Potential ◽

Traumatic Injury ◽

Neuroprotective Effects ◽

Stroke Models ◽

Cultured Cortical Neurons

Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy-5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models. Objective: In this study, the protective effect of perampanel was investigated. Method: The protective effect of perampanel was investigated in an in vitro traumatic neuronal injury (TNI) model in primary cultured cortical neurons. Conclusion: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).

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Neurotherapeutic Effect of Inula britannica var. Chinensis against H2O2-Induced Oxidative Stress and Mitochondrial Dysfunction in Cortical Neurons

Antioxidants ◽

10.3390/antiox10030375 ◽

2021 ◽

Vol 10 (3) ◽

pp. 375

Author(s):

Jin Young Hong ◽

Hyunseong Kim ◽

Junseon Lee ◽

Wan-Jin Jeon ◽

Seung Ho Baek ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Cortical Neurons ◽

Inflammatory Diseases ◽

Neuroprotective Effect ◽

Neuroprotective Effects ◽

Neuronal Viability ◽

Inula Britannica ◽

Oxidative Effects

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.

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Neuroprotective effects of diarylpropionitrile against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons

Neuroscience Letters ◽

10.1016/j.neulet.2014.06.029 ◽

2014 ◽

Vol 578 ◽

pp. 44-49 ◽

Cited By ~ 12

Author(s):

Nirut Suwanna ◽

Wipawan Thangnipon ◽

Rungtip Soi-ampornkul

Keyword(s):

Cortical Neurons ◽

Amyloid Peptide ◽

Neuroprotective Effects ◽

Cultured Cortical Neurons ◽

Β Amyloid ◽

Β Amyloid Peptide

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An Na+/H+ exchanger inhibitor suppresses cellular swelling and neuronal death induced by glutamate in cultured cortical neurons

Brain Edema XII ◽

10.1007/978-3-7091-0651-8_48 ◽

2003 ◽

pp. 223-226 ◽

Cited By ~ 2

Author(s):

Seiji Yamamoto ◽

Y. Matsumoto ◽

Y. Suzuki ◽

T. Tsuboi ◽

S. Terakawa ◽

...

Keyword(s):

Neuronal Death ◽

Cortical Neurons ◽

Cultured Cortical Neurons ◽

Cellular Swelling

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Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by β-amyloid 31-35

British Journal Of Nutrition ◽

10.1017/s0007114509243042 ◽

2009 ◽

Vol 102 (5) ◽

pp. 655-662 ◽

Cited By ~ 39

Author(s):

Huan-Ling Yu ◽

Li Li ◽

Xiao-Hong Zhang ◽

Li Xiang ◽

Jie Zhang ◽

...

Keyword(s):

Folic Acid ◽

Cortical Neuron ◽

Cortical Neurons ◽

Tail Length ◽

Underlying Mechanism ◽

Pcr Analysis ◽

Neuroprotective Effects ◽

Regulated Expression ◽

Cultured Cortical Neurons ◽

Β Amyloid

Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in β-amyloid (Aβ) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Aβ31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

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Neuroprotective Effect of Sodium Orthovanadate on Delayed Neuronal Death after Transient Forebrain Ischemia in Gerbil Hippocampus

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200111000-00003 ◽

2001 ◽

Vol 21 (11) ◽

pp. 1268-1280 ◽

Cited By ~ 73

Author(s):

Takayuki Kawano ◽

Kohji Fukunaga ◽

Yusuke Takeuchi ◽

Motohiro Morioka ◽

Shigetoshi Yano ◽

...

Keyword(s):

Neuronal Death ◽

Neuroprotective Effect ◽

Delayed Neuronal Death ◽

Intraventricular Injection ◽

Mongolian Gerbils ◽

Sodium Orthovanadate ◽

Forebrain Ischemia ◽

Neuroprotective Effects ◽

Transient Forebrain Ischemia ◽

Ca1 Region

In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti–phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti–phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.

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Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

10.21203/rs.3.rs-29059/v3 ◽

2021 ◽

Author(s):

Xiao Yan Sheng ◽

Shui Yuan Yang ◽

Xiao Min Wen ◽

Xin Zhang ◽

Yong Feng Ye ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Motor Behavior ◽

Neuroprotective Effect ◽

Signal Pathway ◽

Dopamine Neurons ◽

Therapeutic Modality ◽

Neuroprotective Effects

Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

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