Prolactin prevents mitochondrial dysfunction induced by glutamate excitotoxicity in hippocampal neurons

2019 ◽  
Vol 701 ◽  
pp. 58-64 ◽  
Author(s):  
N.A. Rivero-Segura ◽  
Ma. I. Coronado-Mares ◽  
R. Rincón-Heredia ◽  
I. Pérez-Torres ◽  
T. Montiel ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Hippocampal Neurons ◽  
Glutamate Excitotoxicity

Spatiotemporal resolution of BDNF neuroprotection against glutamate excitotoxicity in cultured hippocampal neurons

Neuroscience ◽  
2013 ◽  
Vol 237 ◽  
pp. 66-86 ◽  
Author(s):  
C.V. Melo ◽  
S. Okumoto ◽  
J.R. Gomes ◽  
M.S. Baptista ◽  
B.A. Bahr ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Glutamate Excitotoxicity ◽  
Spatiotemporal Resolution ◽  
Cultured Hippocampal Neurons

scholarly journals Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons

2019 ◽  
Vol 21 (1) ◽  
pp. 220 ◽  
Author(s):  
Han-A Park ◽  
Nelli Mnatsakanyan ◽  
Katheryn Broman ◽  
Abigail U. Davis ◽  
Jordan May ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Mitochondrial Membrane ◽  
Antioxidant Properties ◽  
B Cell Lymphoma ◽  
Atp Depletion ◽  
Primary Hippocampal Neurons

B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival.

scholarly journals Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Aβ-Exposed Hippocampal Neurons

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Nora E. Gray ◽  
Jonathan A. Zweig ◽  
Donald G. Matthews ◽  
Maya Caruso ◽  
Joseph F. Quinn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Neuroblastoma Cells ◽  
Water Extract ◽  
Centella Asiatica ◽  
Antioxidant Response ◽  
And Oxidative Stress

Centella asiatica has been used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) protects against the deleterious effects of amyloid-β (Aβ) in neuroblastoma cells and attenuates Aβ-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals. This study investigates the effects of CAW on neuronal metabolism and oxidative stress in isolated Aβ-expressing neurons. Hippocampal neurons from amyloid precursor protein overexpressing Tg2576 mice and wild-type (WT) littermates were treated with CAW. In both genotypes, CAW increased the expression of antioxidant response genes which attenuated the Aβ-induced elevations in reactive oxygen species (ROS) and lipid peroxidation in Tg2576 neurons. CAW also improved mitochondrial function in both genotypes and increased the expression of electron transport chain enzymes and mitochondrial labeling, suggesting an increase in mitochondrial content. These data show that CAW protects against mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons which could contribute to the beneficial effects of the extract observed in vivo. Since CAW also improved mitochondrial function in the absence of Aβ, these results suggest a broader utility for other conditions where neuronal mitochondrial dysfunction occurs.

scholarly journals Anesthetic Protection of Neurons Injured by Hypothermia and Rewarming

2012 ◽  
Vol 117 (2) ◽  
pp. 280-292 ◽  
Author(s):  
Philip E. Bickler ◽  
Daniel E. Warren ◽  
John P. Clark ◽  
Pablo Gabatto ◽  
Maren Gregersen ◽  
...  
Keyword(s):  
Cell Death ◽  
Hippocampal Neurons ◽  
Mild Hypothermia ◽  
Culture Media ◽  
Glutamate Excitotoxicity ◽  
Cell Swelling ◽  
Profound Hypothermia ◽  
Anesthetic Agents ◽  
Aspartate Receptor ◽  
Hypoxia Ischemia

Background Mild hypothermia is neuroprotective after cerebral ischemia but surgery involving profound hypothermia (PH, temperature less than 18°C) is associated with neurologic complications. Rewarming (RW) from PH injures hippocampal neurons by glutamate excitotoxicity, N-methyl-D-aspartate receptors, and intracellular calcium. Because neurons are protected from hypoxia-ischemia by anesthetic agents that inhibit N-methyl-D-aspartic acid receptors, we tested whether anesthetics protect neurons from damage caused by PH/RW. Methods Organotypic cultures of rat hippocampus were used to model PH/RW injury, with hypothermia at 4°C followed by RW to 37°C and assessment of cell death 1 or 24 h later. Cell death and intracellular Ca were assessed with fluorescent dye imaging and histology. Anesthetic agents were present in the culture media during PH and RW or only RW. Results Injury to hippocampal CA1, CA3, and dentate neurons after PH and RW involved cell swelling, cell rupture, and adenosine triphosphate (ATP) loss; this injury was similar for 4 through 10 h of PH. Isoflurane (1% and 2%), sevoflurane (3%) and xenon (60%) reduced cell loss but propofol (3 μM) and pentobarbital (100 μM) did not. Isoflurane protection involved reduction in N-methyl-D-aspartate receptor-mediated Ca influx during RW but did not involve γ-amino butyric acid receptors or KATP channels. However, cell death increased over the next day. Conclusion Anesthetic protection of neurons rewarmed from 4°C involves suppression of N-methyl-D-aspartate receptor-mediated Ca overload in neurons undergoing ATP loss and excitotoxicity. Unlike during hypoxia/ischemia, anesthetic agents acting predominantly on γ-aminobutyric acid receptors do not protect against PH/RW. The durability of anesthetic protection against cold injury may be limited.

scholarly journals eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects

2020 ◽  
Author(s):  
Ariel Caviedes ◽  
Barbara Maturana ◽  
Katherina Corvalán ◽  
Alexander Engler ◽  
Felipe Gordillo ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Protein S ◽  
Subcellular Fractionation ◽  
Glutamate Excitotoxicity ◽  
Luciferase Reporter ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Neuroprotective Effects ◽  
Biotin Switch

AbstractCell death by glutamate excitotoxicity, mediated by N-methyl-D-aspartate (NMDA) receptors, negatively impacts brain function, including but not limited to hippocampal neurons. The NF-κB transcription factor (composed mainly of p65/p50 subunits) contributes to neuronal death in excitotoxicity, while its inhibition should improve cell survival. Using the biotin switch method, subcellular fractionation, immunofluorescence and luciferase reporter assays, we found that NMDA stimulated NF-κB activity selectively in hippocampal neurons, while endothelial nitric oxide synthase (eNOS), an enzyme expressed in neurons, is involved in the S-nitrosylation of p65 and consequent NF-κB inhibition in cerebrocortical, i.e., resistant neurons. The S-nitro proteomes of cortical and hippocampal neurons revealed that different biological processes are regulated by S-nitrosylation in susceptible and resistant neurons, bringing to light that protein S-nitrosylation is a ubiquitous post-translational modification, able to influence a variety of biological processes including the homeostatic inhibition of the NF-κB transcriptional activity in cortical neurons exposed to NMDA receptor overstimulation.

scholarly journals Inhibition of Mg2+ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2768
Author(s):  
Yutaka Shindo ◽  
Ryu Yamanaka ◽  
Kohji Hotta ◽  
Kotaro Oka
Keyword(s):  
Nervous System ◽  
Steady State ◽  
Hippocampal Neurons ◽  
Neuronal Survival ◽  
Glutamate Excitotoxicity ◽  
Cellular Energy ◽  
Toxic Concentration ◽  
The Central Nervous System ◽  
Steady State Levels ◽  
High Concentrations

Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity.

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