Spare respiratory capacity, oxidative stress and excitotoxicity

2009 ◽  
Vol 37 (6) ◽  
pp. 1385-1388 ◽  
Author(s):  
David G. Nicholls
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Chronic Exposure ◽  
Neuronal Damage ◽  
Glutamate Excitotoxicity ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Respiratory Capacity

Chronic exposure to glutamate (glutamate excitotoxicity) exacerbates neuronal damage in the aftermath of stroke and is implicated in a variety of neurodegenerative disorders. Mitochondria play a central role in the survival or death of the exposed neuron. Calcium, oxidative stress and ATP insufficiency play closely interlocked roles that may be investigated with primary neuronal cultures.

scholarly journals Oxidative Stress Induces Dephosphorylation of τ in Rat Brain Primary Neuronal Cultures

2002 ◽  
Vol 68 (4) ◽  
pp. 1590-1597 ◽  
Author(s):  
Daniel R. Davis ◽  
Brian H. Anderton ◽  
Jean-Pierre Brion ◽  
C. Hugh Reynolds ◽  
Diane P. Hanger
Keyword(s):  
Oxidative Stress ◽  
Rat Brain ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures

Effect of vitamin D treatment on VDR expression in primary cerebral cortical cells in induced oxidative stress

2020 ◽  
pp. 1-10
Author(s):  
Ebtesam Alsulami ◽  
Majed Alokail ◽  
Amani Alghamedi ◽  
Abir Alamro ◽  
Samina Haq
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Cultured Cells ◽  
Neuroprotective Effect ◽  
Sandwich Elisa ◽  
Stress Protein ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Peripheral Tissues

BACKGROUND: In addition to calcium and phosphate homeostasis in peripheral tissues; vitamin D performs a neuroprotection role in the nervous system. The neuroprotective actions of vitamin D include: increasing vitamin D receptor (VDR) expression, control glutathione synthesis and nitric oxide synthase activity and induce neurotrophins such as nerve growth factor (NGF). VDR mediates cellular actions, and biological responses of the vitamin D. OBJECTIVE: To study the effect of VDR and NGF expression levels by vitamin D3 treatment in induced oxidative stress in primary cortical neuronal cultures. METHOD: Primary neuronal cultures were set up from the cortex region of neonatal rat’s brain. They were cultured for up to 72 h in the presence of 0.25μg/ml vitamin D3. These cells were exposed to 0.5 mM H2O2 for two hours before collecting cell pellet and medium for biochemical assays. Control and H2O2 treated cells were cultured in the absence of vitamin D3 treatment. Sandwich ELISA was used to study NGF expression. Western blotting and Immunofluorescence of cultured cells were used to estimate the expression of VDR. RESULTS: Vitamin D3 treatment increased more significantly (P <  0.001) NGF levels with and without induced oxidative stress. Protein expression studies confirmed the positive correlation between VDR expression and vitamin D3 treatment after 72 h in culture. Moreover, pre-treating the cells with vitamin D3 before H2O2 exposure significantly increase (P <  0.05) VDR expression in comparison with the cells exposed to H2O2 alone. CONCLUSION: The neuroprotective effect of vitamin D3 against oxidative stress could be through up-regulating VDR and NGF levels.

scholarly journals Phosphorylation of p66Shc and forkhead proteins mediates Aβ toxicity

2005 ◽  
Vol 169 (2) ◽  
pp. 331-339 ◽  
Author(s):  
Wanli W. Smith ◽  
Darrell D. Norton ◽  
Myriam Gorospe ◽  
Haibing Jiang ◽  
Shino Nemoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Regulation ◽  
Critical Role ◽  
Ectopic Expression ◽  
Amyloid Β ◽  
Dominant Negative ◽  
Neuronal Cultures ◽  
Amyloid Β Peptide ◽  
Dependent Manner ◽  
Primary Neuronal Cultures

Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Aβ induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Aβ toxicity. Treatment of cells and primary neuronal cultures with Aβ caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative SEK1 mutant or chemical JNK inhibition reduced Aβ-induced JNK activation and p66Shc phosphorylation (Ser36), suggesting that JNK phosphorylates p66Shc. Aβ induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against Aβ-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies Aβ toxicity. These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD.

scholarly journals DNA strand breaks induced by sustained glutamate excitotoxicity in primary neuronal cultures

1996 ◽  
Vol 16 (7) ◽  
pp. 2238-2250 ◽  
Author(s):  
M Didier ◽  
S Bursztajn ◽  
E Adamec ◽  
L Passani ◽  
RA Nixon ◽  
...  
Keyword(s):  
Dna Strand Breaks ◽  
Glutamate Excitotoxicity ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Strand Breaks ◽  
Dna Strand

scholarly journals Neuroprotective Effect of Gallocatechin Gallate on Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1387
Author(s):  
Do Hwi Park ◽  
Jun Yeon Park ◽  
Ki Sung Kang ◽  
Gwi Seo Hwang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Nuclear Condensation ◽  
Epicatechin Gallate ◽  
Ht22 Cells ◽  
Gallocatechin Gallate

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

2014 ◽  
Vol 121 (6) ◽  
pp. 1424-1431 ◽  
Author(s):  
Joshua D. Bell ◽  
Theresa Currier Thomas ◽  
Elliot Lass ◽  
Jinglu Ai ◽  
Hoyee Wan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Glutamate Receptor ◽  
Neuronal Damage ◽  
Platelet Rich Plasma ◽  
Receptor Expression ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Neuronal Viability ◽  
Activated Platelets

Object Glutamate is important in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Notably, brain extracellular and cerebrospinal fluid as well as blood glutamate concentrations increase after experimental and clinical trauma. While neurons are one potential source of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. This study investigates the hypothesis that platelet microthrombi release glutamate that mediates excitotoxic brain injury and neuron dysfunction after subarachnoid hemorrhage (SAH). Methods The authors used two models, primary neuronal cultures exposed to activated platelets, as well as a whole-animal SAH preparation. Propidium iodide was used to evaluate neuronal viability, and surface glutamate receptor staining was used to evaluate the phenotype of platelet-exposed neurons. Results The authors demonstrate that thrombin-activated platelet-rich plasma releases glutamate, at concentrations that can exceed 300 μM. When applied to neuronal cultures, this activated plasma is neurotoxic, and the toxicity is attenuated in part by glutamate receptor antagonists. The authors also demonstrate that exposure to thrombin-activated platelets induces marked downregulation of the surface glutamate receptor glutamate receptor 2, a marker of excitotoxicity exposure and a possible mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days after SAH in rats there was a strong correlation between proximity to microthrombi and reduction of surface glutamate receptors. Conclusions The authors conclude that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might mediate brain injury after SAH.

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