Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury

Chen, Tao; Wu, Yu; Wang, Yuzi; Zhu, Jiang; Chu, Haiying; Kong, Li; Yin, Liangwei; Ma, Haiying

doi:10.1007/s11064-017-2340-7

Cited by 53 publications

(30 citation statements)

References 53 publications

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“…By binding to tropomyosin receptor kinase (Trk) receptors, BDNF and NGF activate the downstream signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) [43, 44]. Several lines of evidence reported that Nrf2 activation can be regulated via PI3K/Akt and MAPK/ERK pathways and thereby affects redox homeostasis [17, 19, 45–47]. Some studies suggested that BDNF can active antioxidant mechanisms constantly by inducing Nrf2 nuclear translocation [18].…”

Section: Discussionmentioning

confidence: 99%

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

Liu

et al. 2018

Oxidative Medicine and Cellular Longevity

100

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The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2′-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of UA were markedly inhibited by administration of brusatol, an inhibitor of Nrf2. Taken together, the antioxidant and neuroprotective effects afforded by UA treatment involved the modulation of Nrf2-mediated oxidative stress and regulation of BDNF and NGF expression levels. Thus, UA treatment could be of interest to prevent FCI/R injury.

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Section: Discussionmentioning

confidence: 99%

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

Liu

et al. 2018

Oxidative Medicine and Cellular Longevity

100

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“…The blots were washed with TBST three times for 10 min each, incubated for 1 h with horseradish peroxidase-conjugated goat anti-rabbit or goat anti-mouse IgG (1 : 5000; ZSGB-Bio, China), and washed with TBST three times for 10 min each. The bound antibodies were detected by chemiluminescence using an ECL Western blotting detection system kit (GE Amersham Biosciences, Buckinghamshire, UK) and exposed to ChemiDOC™ XRS+ Image Lab™ Software (Bio-Rad Laboratories, Inc., Hercules, CA, USA) [46].…”

Section: Ros Staining and Fluorescence Microscopymentioning

confidence: 99%

TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways

Meng

Zhang

Guo

et al. 2020

Oxidative Medicine and Cellular Longevity

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Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.

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“…Both the NF-B and MAPK immunomodulatory pathways strongly regulate the expression of diverse cytokines involved in immune responses, like microglial activation and recruitment [e.g., macrophage-colony-stimulating factor (M-CSF), MCP-1; Hommes et al, 2003;Cloutier et al, 2007;Liu et al, 2017]. These pathways also control the expression of neurotrophic and synaptotrophic factors and are involved in mechanisms of learning and memory (Sweatt, 2001;Kaltschmidt et al, 2006;Mattson and Meffert, 2006;Chen et al, 2017). Recent stud-ies have shown 40 Hz flicker changes protein phosphorylation patterns after weeks of exposure compared with no stimulation, but the immediate effect of flicker on protein phosphorylation in general and the immediate effects of flicker on these two key phosphoprotein pathways are still unknown (Adaikkan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Gamma Visual Stimulation Induces a Neuroimmune Signaling Profile Distinct from Acute Neuroinflammation

et al. 2019

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Many neurodegenerative and neurological diseases are rooted in dysfunction of the neuroimmune system; therefore, manipulating this system has strong therapeutic potential. Prior work has shown that exposing mice to flickering lights at 40 Hz drives gamma frequency (ϳ40 Hz) neural activity and recruits microglia, the primary immune cells of the brain, revealing a novel method to manipulate the neuroimmune system. However, the biochemical signaling mechanisms between 40 Hz neural activity and immune recruitment remain unknown. Here, we exposed wild-type male mice to 5-60 min of 40 Hz or control flicker and assessed cytokine and phosphoprotein networks known to play a role in immune function. We found that 40 Hz flicker leads to increases in the expression of cytokines which promote microglial phagocytic states, such as IL-6 and IL-4, and increased expression of microglial chemokines, such as macrophagecolony-stimulating factor and monokine induced by interferon-␥. Interestingly, cytokine effects differed as a function of stimulation frequency, revealing a range of neuroimmune effects of stimulation. To identify possible mechanisms underlying cytokine expression, we quantified the effect of the flicker on intracellular signaling pathways known to regulate cytokine levels. We found that a 40 Hz flicker upregulates phospho-signaling within the nuclear factor-light-chain-enhancer of activated B cells (NF-B) and mitogen-activated protein kinase (MAPK) pathways. While cytokine expression increased after 1 h of 40 Hz flicker stimulation, protein phosphorylation in the NF-B pathway was upregulated within minutes. Importantly, the cytokine expression profile induced by 40 Hz flicker was different from cytokine changes in response to acute neuroinflammation induced by lipopolysaccharides. These results are the first, to our knowledge, to show how visual stimulation rapidly induces critical neuroimmune signaling in healthy animals.

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Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury

Cited by 53 publications

References 53 publications

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways

Gamma Visual Stimulation Induces a Neuroimmune Signaling Profile Distinct from Acute Neuroinflammation

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