scholarly journals Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 603
Author(s):  
Hyunseong Kim ◽  
Jin Young Hong ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
In-Hyuk Ha
Keyword(s):  
Phospholipase A2 ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neurological Diseases ◽  
Minor Component ◽  
Underlying Mechanism ◽  
Bee Venom ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Wide Range

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

scholarly journals PDGF Suppresses Oxidative Stress Induced Ca2+Overload and Calpain Activation in Neurons

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Lian-Shun Zheng ◽  
Yoko Ishii ◽  
Qing-Li Zhao ◽  
Takashi Kondo ◽  
Masakiyo Sasahara
Keyword(s):  
Oxidative Stress ◽  
Map Kinases ◽  
Neurological Diseases ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Calpain Activation ◽  
Neurotoxic Effects ◽  
Nonapoptotic Cell Death ◽  
Dose Dependent

Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. We previously demonstrated that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an underlying mechanism. Ca2+overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs on H2O2-induced Ca2+overload in primary cultured neurons to further clarify their neuroprotective mechanism. H2O2-induced Ca2+overload in neurons in a dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. We then evaluated calpain activation, which was induced by Ca2+overload and mediated both apoptotic and nonapoptotic cell death. H2O2-induced calpain activation in neurons in a dose-dependent manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain activation. To the best of our knowledge, the present study is the first to demonstrate the mechanism underlying the neuroprotective effects of PDGF against oxidative stress via the suppression of Ca2+overload and inactivation of calpain and suggests that PDGF-BB may be a potential therapeutic target of neurological diseases.

scholarly journals CIRBP Ameliorates Neuronal Amyloid Toxicity via Antioxidative and Antiapoptotic Pathways in Primary Cortical Neurons

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Fang Su ◽  
Shanshan Yang ◽  
Hongcai Wang ◽  
Zhenkui Qiao ◽  
Hong Zhao ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Rna Binding ◽  
Neuronal Loss ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Primary Cortical Neurons ◽  
Amyloid Toxicity ◽  
Proapoptotic Protein ◽  
Ad Prevention

It is generally accepted that the amyloid β (Aβ) peptide toxicity contributes to neuronal loss and is involved in the initiation and progression of Alzheimer’s disease (AD). Cold-inducible RNA-binding protein (CIRBP) is reported to be a general stress-response protein, which is induced by different stress conditions. Previous reports have shown the neuroprotective effects of CIRBP through the suppression of apoptosis via the Akt and ERK pathways. The objective of this study is to examine the effect of CIRBP against Aβ-induced toxicity in cultured rat primary cortical neurons and attempt to uncover its underlying mechanism. Here, MTT, LDH release, and TUNEL assays showed that CIRBP overexpression protected against both intracellular amyloid β- (iAβ-) induced and Aβ25-35-induced cytotoxicity in rat primary cortical neurons. Electrophysiological changes responsible for iAβ-induced neuronal toxicity, including an increase in neuronal resting membrane potentials and a decrease in K+ currents, were reversed by CIRBP overexpression. Western blot results further showed that Aβ25-35 treatment significantly increased the level of proapoptotic protein Bax, cleaved caspase-3, and cleaved caspase-9 and decreased the level of antiapoptotic factor Bcl-2, but were rescued by CIRBP overexpression. Furthermore, CIRBP overexpression prevented the elevation of ROS induced by Aβ25-35 treatment by decreasing the activities of oxidative biomarker and increasing the activities of key enzymes in antioxidant system. Taken together, our findings suggested that CIRBP exerted protective effects against neuronal amyloid toxicity via antioxidative and antiapoptotic pathways, which may provide a promising candidate for amyloid-based AD prevention or therapy.

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

2009 ◽  
Vol 102 (5) ◽  
pp. 655-662 ◽  
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.

Cadmium Inhibits Neurite Outgrowth in Differentiating Human SH-SY5Y Neuroblastoma Cells

2014 ◽  
Vol 33 (5) ◽  
pp. 412-418 ◽  
Author(s):  
Eun Joo Pak ◽  
Gi Dong Son ◽  
Byung Sun Yoo
Keyword(s):  
Neurite Outgrowth ◽  
Neuroblastoma Cells ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cadmium Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Ros Scavenger ◽  
Dose Dependent

Cadmium, a highly ubiquitous heavy metal, is well known to induce neurotoxicity. However, the underlying mechanism of cadmium-mediated neurotoxicity remains unclear. We have studied cadmium inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all- trans-retinoic acid (RA). Cadmium, at a concentration of 3 μmol/L, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells 48 hours after cadmium treatment (1-3 μmol/L cadmium) was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 1 to 3 μmol/L cadmium resulted in decreased level of cross-reactivities with 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The reactive oxygen species (ROS) scavenger, NAC (N-acetyl-l-cysteine), recovered the expression of GAP-43 in cadmium-treated cells. The results indicate that cadmium is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells and that this effect might result from ROS generation by cadmium.

scholarly journals Betulinic Acid Inhibits ROS-Mediated Pyroptosis in Spinal Cord Injury by Augmenting Autophagy via the AMPK-mTOR-TFEB Signaling Pathway

2020 ◽  
Author(s):  
Chenyu Wu ◽  
Huanwen Chen ◽  
Rong Zhuang ◽  
Yongli Wang ◽  
Xinli Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
Neurological Diseases ◽  
Underlying Mechanism ◽  
Autophagy Flux ◽  
Wide Range ◽  
Cord Injury

Abstract Background：Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. Methods：Using a mouse model of SCI, survival and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, and pyroptosis; ROS- and AMPK-related signaling pathways were also examined. Results：Our results showed that BA significantly improves functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS-activity and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induces mitophagy to eliminate the accumulation of ROS and subsequently inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Conclusion: BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

scholarly journals Gongjin-Dan Enhances Neurite Outgrowth of Cortical Neuron by Ameliorating H2O2-Induced Oxidative Damage via Sirtuin1 Signaling Pathway

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4290
Author(s):  
Hyunseong Kim ◽  
Wanjin Jeon ◽  
Jinyoung Hong ◽  
Junseon Lee ◽  
Changhwan Yeo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Neurological Diseases ◽  
Preventive Effect ◽  
Neuroprotective Effects ◽  
Mature Neuron ◽  
Pre Treatment ◽  
And Oxidative Stress

Gongjin-dan (GJD) is a multiherbal formula produced from 10 medicinal herbs and has been traditonally used as an oriental medicine to treat cardiovascular diseases, alcoholic hepatitis, mild dementia, and anemia. Additionally, increasing evidence suggests that GJD exerts neuroprotective effects by suppressing inflammation and oxidative stress-induced events to prevent neurological diseases. However, the mechanism by which GJD prevents oxidative stress-induced neuronal injury in a mature neuron remains unknown. Here, we examined the preventive effect and mechanism of GJD on primary cortical neurons exposed to hydrogen peroxide (H2O2). In the neuroprotection signaling pathway, Sirtuin1 is involved in neuroprotective action as a therapeutic target for neurological diseases. After pre-treatment with GJD at three concentrations (10, 25, and 50 µg/mL) and stimulation by H2O2 (30 µM) for 24 h, the influence of GJD on Sirtuin1 activation was assessed using immunocytochemistry, real-time PCR, western blotting, and flow cytometry. GJD effectively ameliorated H2O2-induced neuronal death against oxidative damage through Sirtuin1 activation. In addition, GJD-induced Sirtuin1 activation accelerated elongation of new axons and formation of synapses via increased expression of nerve growth factor and brain-derived neurotrophic factor, as well as regeneration-related genes. Thus, GJD shows potential for preventing neurological diseases via Sirtuin1 activation.

scholarly journals Guanosine modulates SUMO2/3-ylation in neurons and astrocytes via adenosine receptors

2020 ◽  
Vol 16 (3) ◽  
pp. 439-450
Author(s):  
Camila A. Zanella ◽  
Carla I. Tasca ◽  
Jeremy M. Henley ◽  
Kevin A. Wilkinson ◽  
Helena I. Cimarosti
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Attractive Potential ◽  
Receptor Interaction ◽  
Post Translational Modification ◽  
Neuroprotective Effects ◽  
Adenosine Receptor Antagonist ◽  
Wide Range

Abstract SUMOylation is a post-translational modification (PTM) whereby members of the Small Ubiquitin-like MOdifier (SUMO) family of proteins are conjugated to lysine residues in target proteins. SUMOylation has been implicated in a wide range of physiological and pathological processes, and much attention has been given to its role in neurodegenerative conditions. Due to its reported role in neuroprotection, pharmacological modulation of SUMOylation represents an attractive potential therapeutic strategy in a number of different brain disorders. However, very few compounds that target the SUMOylation pathway have been identified. Guanosine is an endogenous nucleoside with important neuromodulatory and neuroprotective effects. Experimental evidence has shown that guanosine can modulate different intracellular pathways, including PTMs. In the present study we examined whether guanosine alters global protein SUMOylation. Primary cortical neurons and astrocytes were treated with guanosine at 1, 10, 100, 300, or 500 μM at four time points, 1, 6, 24, or 48 h. We show that guanosine increases global SUMO2/3-ylation in neurons and astrocytes at 1 h at concentrations above 10 μM. The molecular mechanisms involved in this effect were evaluated in neurons. The guanosine-induced increase in global SUMO2/3-ylation was still observed in the presence of dipyridamole, which prevents guanosine internalization, demonstrating an extracellular guanosine-induced effect. Furthermore, the A1 adenosine receptor antagonist DPCPX abolished the guanosine-induced increase in SUMO2/3-ylation. The A2A adenosine receptor antagonist ZM241385 increased SUMOylation per se, but did not alter guanosine-induced SUMOylation, suggesting that guanosine may modulate SUMO2/3-ylation through an A1-A2A receptor interaction. Taken together, this is the first report to show guanosine as a SUMO2/3-ylation enhancer in astrocytes and neurons.

scholarly journals Fingolimod Modulates Dendritic Architecture in a BDNF-Dependent Manner

2020 ◽  
Vol 21 (9) ◽  
pp. 3079 ◽  
Author(s):  
Abhisarika Patnaik ◽  
Eleonora Spiombi ◽  
Angelisa Frasca ◽  
Nicoletta Landsberger ◽  
Marta Zagrebelsky ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Rett Syndrome ◽  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Neurological Diseases ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Spine Density ◽  
Neuronal Structure ◽  
Cellular Mechanisms

The brain-derived neurotrophic factor (BDNF) plays crucial roles in both the developing and mature brain. Moreover, alterations in BDNF levels are correlated with the cognitive impairment observed in several neurological diseases. Among the different therapeutic strategies developed to improve endogenous BDNF levels is the administration of the BDNF-inducing drug Fingolimod, an agonist of the sphingosine-1-phosphate receptor. Fingolimod treatment was shown to rescue diverse symptoms associated with several neurological conditions (i.e., Alzheimer disease, Rett syndrome). However, the cellular mechanisms through which Fingolimod mediates its BDNF-dependent therapeutic effects remain unclear. We show that Fingolimod regulates the dendritic architecture, dendritic spine density and morphology of healthy mature primary hippocampal neurons. Moreover, the application of Fingolimod upregulates the expression of activity-related proteins c-Fos and pERK1/2 in these cells. Importantly, we show that BDNF release is required for these actions of Fingolimod. As alterations in neuronal structure underlie cognitive impairment, we tested whether Fingolimod application might prevent the abnormalities in neuronal structure typical of two neurodevelopmental disorders, namely Rett syndrome and Cdk5 deficiency disorder. We found a significant rescue in the neurite architecture of developing cortical neurons from Mecp2 and Cdkl5 mutant mice. Our study provides insights into understanding the BDNF-dependent therapeutic actions of Fingolimod.

scholarly journals Robust RBM3 and β-klotho expression in developing neurons in the human brain

2019 ◽  
Vol 39 (12) ◽  
pp. 2355-2367 ◽  
Author(s):  
Travis C Jackson ◽  
Keri Janesko-Feldman ◽  
Shaun W Carlson ◽  
Shawn E Kotermanski ◽  
Patrick M Kochanek
Keyword(s):  
Cortical Neurons ◽  
Rna Binding ◽  
Transmembrane Protein ◽  
Adult Brain ◽  
Human Infant ◽  
Fibroblast Growth Factor 21 ◽  
Binding Motif ◽  
Dependent Manner ◽  
Neuroprotective Effects

RNA binding motif 3 (RBM3) is a powerful neuroprotectant that inhibits neurodegenerative cell death in vivo and is a promising therapeutic target in brain ischemia. RBM3 is increased by the hormone fibroblast growth factor 21 (FGF21) in an age- and temperature-dependent manner in rat cortical neurons. FGF21 receptor binding is controlled by the transmembrane protein β-klotho, which is mostly absent in the adult brain. We discovered that RBM3/β-klotho is unexpectedly high in the human infant vs. adult brain (hippocampus/prefrontal cortex). The use of tissue homogenates in that study precluded a comparison of RBM3/β-klotho expression among different CNS cell-types, thus, omitted key evidence (i.e. confirmation of neuronal expression) that would otherwise provide a critical link to support their possible direct neuroprotective effects in humans. This report addresses that knowledge gap. High-quality fixed human hippocampus, cortex, and hypothalamic tissues were acquired from the NIH Neurobiobank (<1 yr (premature born) infants, 1 yr, 4 yr, and 34 yr). Dual labeling of cell-type markers vs. RBM3/β-klotho revealed enriched staining of targets in neurons in the developing brain. Identifying that RBM3/β-klotho is abundant in neurons in the immature brain is fundamentally important to guide protocol design and conceptual frameworks germane to future testing of these neuroprotective pathways in humans.

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