scholarly journals Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway

2019 ◽  
Vol 20 (4) ◽  
pp. 998 ◽  
Author(s):  
Yao-Chung Chuang ◽  
Shang-Der Chen ◽  
Chung-Yao Hsu ◽  
Shu-Fang Chen ◽  
Nai-Ching Chen ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Signaling Pathway ◽  
Mitochondrial Biogenesis ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Prolonged Seizure

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known to regulate mitochondrial biogenesis. Resveratrol is present in a variety of plants, including the skin of grapes, blueberries, raspberries, mulberries, and peanuts. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, stroke, and epilepsy. This study examined the neuroprotective effect of resveratrol on mitochondrial biogenesis in the hippocampus following experimental status epilepticus. Kainic acid was microinjected into left hippocampal CA3 in Sprague Dawley rats to induce bilateral prolonged seizure activity. PGC-1α expression and related mitochondrial biogenesis were investigated. Amounts of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), cytochrome c oxidase 1 (COX1), and mitochondrial DNA (mtDNA) were measured to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis machinery after prolonged seizure were found in CA3. Resveratrol increased expression of PGC-1α, NRF1, and Tfam, NRF1 binding activity, COX1 level, and mtDNA amount. In addition, resveratrol reduced activated caspase-3 activity and attenuated neuronal cell damage in the hippocampus following status epilepticus. These results suggest that resveratrol plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1α signaling pathway.

scholarly journals Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus

2019 ◽  
Vol 20 (14) ◽  
pp. 3588 ◽  
Author(s):  
Yao-Chung Chuang ◽  
Shang-Der Chen ◽  
Shuo-Bin Jou ◽  
Tsu-Kung Lin ◽  
Shu-Fang Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Status Epilepticus ◽  
Mitochondrial Biogenesis ◽  
Cell Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Sirtuin 1 ◽  
Antisense Oligodeoxynucleotide ◽  
Peroxisome Proliferator ◽  
Sprague Dawley

Status epilepticus may decrease mitochondrial biogenesis, resulting in neuronal cell death occurring in the hippocampus. Sirtuin 1 (SIRT1) functionally interacts with peroxisome proliferator-activated receptors and γ coactivator 1α (PGC-1α), which play a crucial role in the regulation of mitochondrial biogenesis. In Sprague-Dawley rats, kainic acid was microinjected unilaterally into the hippocampal CA3 subfield to induce bilateral seizure activity. SIRT1, PGC-1α, and other key proteins involving mitochondrial biogenesis and the amount of mitochondrial DNA were investigated. SIRT1 antisense oligodeoxynucleotide was used to evaluate the relationship between SIRT1 and mitochondrial biogenesis, as well as the mitochondrial function, oxidative stress, and neuronal cell survival. Increased SIRT1, PGC-1α, and mitochondrial biogenesis machinery were found in the hippocampus following experimental status epilepticus. Downregulation of SIRT1 decreased PGC-1α expression and mitochondrial biogenesis machinery, increased Complex I dysfunction, augmented the level of oxidized proteins, raised activated caspase-3 expression, and promoted neuronal cell damage in the hippocampus. The results suggest that the SIRT1 signaling pathway may play a pivotal role in mitochondrial biogenesis, and could be considered an endogenous neuroprotective mechanism counteracting seizure-induced neuronal cell damage following status epilepticus.

scholarly journals Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Fang Xian ◽  
Zhi-Xiu Lin ◽  
Qing-Qiu Mao ◽  
Jian-Nan Chen ◽  
Zi-Ren Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Protective Effects ◽  
Phosphorylated Akt ◽  
Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

scholarly journals The combination of Acalypha indica–Centella asiatica extracts decreases the neuronal damage in hypoxia-induced hippocampal injury animal model

2018 ◽  
Vol 27 (3) ◽  
pp. 137-44
Author(s):  
Siti Farida ◽  
Desak G.B. Krisnamurti ◽  
Ninik Mudjihartini ◽  
Erni H. Purwaningsih ◽  
Imelda M. Sianipar ◽  
...  
Keyword(s):  
Animal Model ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Centella Asiatica ◽  
Nerve Cells ◽  
Control Treatment ◽  
Control Group ◽  
Sprague Dawley ◽  
Acalypha Indica

Background: Approximately 80–85% of strokes are ischemic and lead to alterations in neuronal cell morphology and cell death. There is a lack of studies on the effect of the combination of Acalypha indica L. (AI) and Centella asiatica L. (CA) in terms of its neurotherapy property. This study was conducted to investigate the neurotherapeutic effect of the combination of AI–CA extracts in improving rat’s hippocampal neuron injury post-hypoxia.Methods: A total of 36 Sprague-Dawley rats were categorized into six groups and placed in a hypoxia chamber for 7 consecutive days. Then, they were moved to normoxia cages and treated for 7 consecutive days as follows: control group without treatment as a negative control; treatment groups were administered citicoline 50 mg/kgBW as a positive control; three different dose combinations of AI150–CA150, AI200–CA150, and AI250–CA150 mg/kgBW, respectively. Histological analyses were performed to assess the improvement in nerve cell damage in the hippocampus.Results: Treatment with citicoline significantly decreased the damage of nerve cells (30.8%); the combination of the AI–CA extracts of AI150–CA150, AI200–CA150, and AI250–CA150 also significantly decreased the damage of nerve cells (36%, 36.4%, and 30.4%, respectively) compared to the control rats (15.4%).Conclusion: The combination of AI–CA extracts decreased the neuronal damage in the hypoxia-induced hippocampal injury animal model. The improvement effect of the combination of AI–CA extracts was not significantly different to citicoline.

Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

2020 ◽  
Author(s):  
Shao-Peng Lin ◽  
Jue-Xian Wei ◽  
Shan Ye ◽  
Jiasong Hu ◽  
Jingyi Bu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Neurocognitive Deficits ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats

1996 ◽  
Vol 80 (2) ◽  
pp. 680-684 ◽  
Author(s):  
T. Y. Kao ◽  
M. T. Lin
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Survival Time ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Serotonin Release ◽  
Brain Serotonin ◽  
Serotonin Depletion

To explore the importance of brain serotonin (5-hydroxytryptamine) in the heatstroke-induced cerebral ischemia and neuronal injury, we evaluated the effects of heatstroke on brain serotonin release, survival time, cerebral hemodynamic changes, and neuronal cell damage in rats with or without brain serotonin depletion produced by 5,7-dihydroxytryptamine. In vivo voltammetry was used to measure changes in extracellular concentrations of serotonin in the anterior hypothalamus, striatum, and frontal cortex. After the onset of heatstroke, rats without brain serotonin depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased cerebral blood flow, increased cerebral serotonin release, and increased cerebral neuronal damage compared with those of normothermic control rats. However, when the cerebral serotonin system was destroyed by 5,7-dihydroxytryptamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the brain, and elevated cerebral serotonin release were reduced. In addition, the survival time of the heatstroke rats was prolonged after the depletion of brain serotonin. The data indicate that brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.

Changes in Extracellular Glutamate Release on Repetitive Transient Occlusion in Global Ischemia Model

2009 ◽  
Author(s):  
Gija Lee ◽  
Seokkeun Choi ◽  
Sungwook Kang ◽  
Samjin Choi ◽  
Jeonghoon Park ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Glutamate Release ◽  
Short Interval ◽  
Neuronal Cell ◽  
Release Time ◽  
Protective Mechanism ◽  
Time Interval ◽  
Extracellular Glutamate ◽  
Vessel Occlusion ◽  
Doppler Flowmetry

During the operation, surgeons in neurosurgical area usually performed the multiple temporary occlusions of parental artery which may induce the neuronal damage. It is generally thought that neuronal damage by cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. In this experiment, we measured the dynamics of extracellular glutamate release in 11 vessel occlusion (VO) model during repeated within short interval. Changes in cerebral blood flow were monitored by laser-Doppler flowmetry simultaneously with cortical glutamate level measured by amperometric biosensor. During ischemia, the peak level of glutamate release was gradually decreased as 112.38±26.21 μM in first period, 82.63±18.50 μM in second period, and 48.58±11.89 μM in third period. The time interval between the ischemia induction and the beginning of glutamate release was increased as 106.7 ± 10.89 (sec) at first attack, 139.11 ± 3.87 (sec) in second attack, 169.00 ± 14.56 (sec) in third ischemic period. From the results of real-time monitoring about glutamate release in 11-VO model during repetitive ischemic episode, it was demonstrated that repetitive ischemia induced less glutamate release from neuronal cell than single ischemia due to endogeneous protective mechanism which delayed glutamate release time in later ischemic injury.

scholarly journals Emodin Alleviates Hydrogen Peroxide-Induced Inflammation and Oxidative Stress via Mitochondrial Dysfunction by Inhibiting the PI3K/mTOR/GSK3β Pathway in Neuroblastoma SH-SY5Y Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rui Li ◽  
Wenzhou Liu ◽  
Li Ou ◽  
Feng Gao ◽  
Min Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Neuroblastoma Cells ◽  
Inflammatory Factors ◽  
Protective Mechanism ◽  
Human Neuroblastoma ◽  
Induced Apoptosis

Emodin is an active monomer extracted from rhubarb root, which has many biological functions, including anti-inflammation, antioxidation, anticancer, and neuroprotection. However, the protective effect of emodin on nerve injury needs to be further elucidated. The purpose of this study is to investigate the effect of emodin on the neuroprotection and the special molecular mechanism. Here, the protective activity of emodin inhibiting H2O2-induced apoptosis and neuroinflammation as well as its molecular mechanisms was examined using human neuroblastoma cells (SH-SY5Y cells). The results showed that emodin significantly enhanced cell viability, reduced cell apoptosis and LDH release. Simultaneously, emodin downregulated H2O2-induced inflammatory factors, including IL-6, NO, and TNF-α, and alleviated H2O2-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. In addition, emodin inhibited the activation of the PI3K/mTOR/GSK3β signaling pathway. What is more, the PI3K/mTOR/GSK3β pathway participated in the protective mechanism of emodin on H2O2-induced cell damage. Collectively, it suggests that emodin alleviates H2O2-induced apoptosis and neuroinflammation potentially by regulating the PI3K/mTOR/GSK3β signaling pathway.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

scholarly journals DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Tao Tao ◽  
Guang-Jie Liu ◽  
Xuan Shi ◽  
Yan Zhou ◽  
Yue Lu ◽  
...  
Keyword(s):  
Subarachnoid Haemorrhage ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Early Brain Injury ◽  
Protective Effects ◽  
In Vivo Models ◽  
The Brain

Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.

Beneficial Effect of Flavone Derivatives on Aβ-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α

2015 ◽  
Vol 34 (3) ◽  
pp. 274-283 ◽  
Author(s):  
Farshad Arsalandeh ◽  
Shahin Ahmadian ◽  
Forough Foolad ◽  
Fariba Khodagholi ◽  
Mahdi M. Farimani ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4′-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4′-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aβ)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aβ injection. Seven days after Aβ administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.

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