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.

Effects of hypercapnia and hypoxia on inspiratory and expiratory diaphragmatic activity in conscious cats

1994 ◽  
Vol 77 (4) ◽  
pp. 1644-1652 ◽  
Author(s):  
M. Bonora ◽  
M. Boule
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Steady State ◽  
Electromyographic Activity ◽  
Large Reduction ◽  
Before And After ◽  
The Central Nervous System ◽  
State Changes ◽  
Chemical Stimuli ◽  
Adult Cats

The influence of steady-state changes in chemical stimuli on ventilation and electromyographic activity of the diaphragm during both inspiration (total DI) and expiration (total DE) was studied in unanesthetized intact adult cats before and after carotid denervation. In intact animals, during hypercapnia (2 4, and 6% CO2), tidal volume (VT) and total DI increase, whereas total DE did not consistently change. During ambient hypocapnic hypoxia (14, 12, and 10% O2), VT increased only at 10% O2, whereas total DI increased at all levels studied. Total DE increased substantially at 14% O2, persisting up to the end of expiration with 12 and 10% O2. This effect was markedly attenuated during normocapnic hypoxia. During CO hypoxemia (1,700 ppm in air), VT as well as total DI and total DE decreased because of a large reduction in inspiratory and expiratory time elicited by tachypneic breathing. The effects of hypercapnia and hypoxia persisted after carotid denervation. Therefore, 1) in contrast to hypercapnia, hypoxia markedly enhances the expiratory diaphragmatic activity, 1) this expiratory braking mechanism depends on the severity of hypoxia and is partly due to hypocapnia secondary to hypoxia; and 3) because this effect was observed after carotid denervation and during CO hypoxemia, it may arise in the central nervous system, possibly in bulbopontine structures.

Effect of Nicotine on the Synapse of the Central Nervous System

1958 ◽  
Vol 192 (3) ◽  
pp. 447-452 ◽  
Author(s):  
Sadayuki F. Takagi ◽  
Yutaka Oomura
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Transmission ◽  
Reflex Activity ◽  
Synaptic Delay ◽  
Synaptic Potential ◽  
Before And After ◽  
The Central Nervous System ◽  
High Concentrations

The effect of nicotine on synaptic transmission in the frog and cat spinal cord was studied. Both a regular wick electrode and a microelectrode of the Ling-Gerard type were used. The reflex activity of the bullfrog spinal cord is facilitated by 0.01% nicotine solution, but is depressed and abolished by 0.1% solution. In the cat, intravenous administration of 150 mg/kg fails to block reflex activity, but topical application does block. The intracellular potential, of both frog and cat motoneurones, shows no change in the synaptic potential after application of the drug, but the spike appears after a shorter synaptic delay and one or more additional spikes appear. When the synaptic delay becomes sufficiently short, however, all spikes suddenly disappear, leaving the still unchanged synaptic potential. Occasionally the synaptic delay is again increased just before the spike potentials disappear. The excitability of a frog motoneurone was measured, by a recording microelectrode, before and after nicotine application. The drug first increased and then decreases excitability. Epinephrine can restore a reflex discharge depressed or abolished by nicotine. It is concluded that high concentrations of nicotine block synaptic transmission in the central nervous system, acting on the cell body but not on the synaptic potential.

scholarly journals Interleukin 5 (IL-5) provides a signal that is required in addition to IL-4 for isotype switching to immunoglobulin (Ig) G1 and IgE.

1992 ◽  
Vol 175 (4) ◽  
pp. 973-982 ◽  
Author(s):  
J M Purkerson ◽  
P C Isakson
Keyword(s):  
Steady State ◽  
Conditioned Media ◽  
Interleukin 4 ◽  
Regulation Of Expression ◽  
Isotype Switching ◽  
Interleukin 5 ◽  
Steady State Levels ◽  
High Concentrations

We have examined the contributions of Interleukin 4 (IL-4), IL-5, and other stimuli to the expression of Immunoglobulin G1 (IgG1) and IgE in murine B lymphoblasts activated with anti-Ig. The combination of IL-4 and -5 induced B lymphoblasts to proliferate and to secrete IgM and IgG1. However, an additional stimulus was required along with IL-4 and -5 for induction of IgE secretion. This stimulus was provided by lipopolysaccharides (LPS) or cytokines produced by TC-1 or EL4 cells. In the absence of IL-5, exceptionally high concentrations of IL-4 (greater than 1,000 U/ml) were required to elicit IgG1 and IgE secretion from B lymphoblasts cultured with either LPS or TC-1-conditioned media (CM). To investigate regulation of expression of gamma 1 and epsilon genes by IL-4, -5, and LPS, the requirements for induction of gamma 1 and epsilon germline and productive transcripts were examined. Germline gamma 1, but not epsilon, transcripts were detected in RNA from B lymphoblasts treated with IL-4 and -5 for 48 h. In contrast, both germline gamma 1 and epsilon transcripts could be detected in B lymphoblasts cultured with IL-4 and LPS, and steady state levels of germline gamma 1 transcripts were four- to sevenfold higher in blasts cultured with LPS and IL-4, compared with blasts cultured with IL-4 and -5. LPS enhanced steady state levels of germline transcripts induced by IL-4, but LPS did not promote substantial accumulation of productive gamma 1 and epsilon transcripts. In contrast, IL-5 did not affect steady state levels of germline transcripts stimulated by IL-4, but did markedly increase levels of productive gamma 1 and epsilon transcripts. Thus, lymphokines regulate two distinct events in isotype switching: induction of germline transcripts (IL-4), and production of VDJ-C gamma 1 and VDJ-C epsilon mRNA (IL-5), which leads to secretion of IgG1 and IgE.

scholarly journals 11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons

2002 ◽  
Vol 29 (3) ◽  
pp. 319-325 ◽  
Author(s):  
SM MacKenzie ◽  
M Lai ◽  
CJ Clark ◽  
R Fraser ◽  
CE Gomez-Sanchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Local System ◽  
Model System ◽  
Biochemical Reactions ◽  
Aldosterone Synthase ◽  
Fetal Rat ◽  
The Central Nervous System

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

scholarly journals The ATF6β-calreticulin axis promotes neuronal survival under endoplasmic reticulum stress and excitotoxicity

2021 ◽  
Author(s):  
Dinh Thi Nguyen ◽  
Thuong Manh Le ◽  
Tsuyoshi Hattori ◽  
Mika Takarada-Iemata ◽  
Hiroshi Ishii ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Hippocampal Neurons ◽  
Neuronal Survival ◽  
Binding Capacity ◽  
Critical Role ◽  
Er Stress Response ◽  
The Central Nervous System ◽  
The Brain

AbstractWhile ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of ATF6β is largely unknown. Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin, a molecular chaperone in the ER with a high Ca2+-binding capacity. Calreticulin expression was reduced to ~50% in the central nervous system of Atf6b−/− mice, and restored by ATF6β. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death, which was rescued by ATF6β, calreticulin, Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in hippocampi of Atf6b−/− and Calr+/− mice, and restored by 2-APB and salubrinal. These results suggest that the ATF6β-calreticulin axis plays a critical role in the neuronal survival by improving Ca2+ homeostasis under ER stress.

scholarly journals Constructive Interference in Steady State Imaging in the Central Nervous System

2011 ◽  
Vol 6 (2) ◽  
pp. 138 ◽  
Author(s):  
Fabrício Guimarães Gonçalves ◽  
Lázaro Luis Faria do Amaral ◽  
◽  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Steady State ◽  
Signal To Noise Ratio ◽  
Cranial Nerves ◽  
High Signal ◽  
Constructive Interference ◽  
Spinal Imaging ◽  
The Central Nervous System ◽  
Noise Ratio

Constructive interference in steady state (CISS) is a fully refocused fast-gradient echo sequence that is mainly used in the assessment of the central nervous system. The most important advantages of steady-state imaging are short acquisition times, high signal-to-noise ratio, and better contrast-to-noise ratio. Owing to its cisternographic effect, CISS is useful in the assessment of the cranial nerves, and can also be used when studying cysts, cystic masses, and neurocysticercosis and in hydrocephalus cases. CISS has been shown to be useful in spinal imaging, epecially in cases of arteriovenous malformation and when it is helpful to better characterise intra- and extramedullary cystic abnormalities.

faint sausage encodes a novel extracellular protein of the immunoglobulin superfamily required for cell migration and the establishment of normal axonal pathways in the Drosophila nervous system

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2747-2758 ◽  
Author(s):  
A.C. Lekven ◽  
U. Tepass ◽  
M. Keshmeshian ◽  
V. Hartenstein
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Peripheral Nervous System ◽  
Neuronal Cell ◽  
Protein Product ◽  
Extracellular Protein ◽  
Immunoglobulin Superfamily ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System ◽  
High Concentrations

We examined the structure of the nervous system in Drosophila embryos homozygous for a null mutation in the faint sausage (fas) gene. In the peripheral nervous system (PNS) of fas mutants, neurons fail to delaminate from the ectodermal epithelium; in the central nervous system (CNS), the positions of neuronal cell bodies and glial cells are abnormal and normal axonal pathways do not form. Sequence analysis of fas cDNAs revealed that the fas protein product has characteristics of an extracellular protein and that it is a novel member of the immunoglobulin (Ig) superfamily. In situ hybridization demonstrated that fas transcripts are expressed throughout the embryo but they are in relatively high concentrations in the lateral ectoderm, from which the peripheral nervous system delaminates and in the CNS. Antiserum directed against Fas protein was found to stain neurons but not glia in the CNS. We conclude that fas encodes a protein that, in the developing nervous system, is present on the surface of neurons and is essential for nerve cell migration and the establishment of axonal pathways.

Morphofunctional Indicators of the Effects of Protons on the Central Nervous System

2019 ◽  
pp. 75-81
Author(s):  
К. Ляхова ◽  
K. Lyakhova ◽  
И. Колесникова ◽  
I. Kolesnikova ◽  
Д. Утина ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purkinje Cells ◽  
Hippocampal Neurons ◽  
Morphological Changes ◽  
Early Period ◽  
The State ◽  
High Plasticity ◽  
The Central Nervous System ◽  
Accelerated Protons

Purpose: Investigation of the dose–time–effect dependency of the behavior of mice and rats after irradiation with accelerated protons and comparison of these data with the morphological changes in the hippocampus and the cerebellum of rodents. Material and methods: Experiments were performed on outbred adult female ICR mice (CD-1), SPF categories, body weight 30–35 g, of the age of 10 weeks – total number 61 animals, and on 39 male Sprague Dawley outbred rats weighing 190–230 g, aged 6.5–7.5 weeks. The animals were irradiated with accelerated protons with energy of 70 MeV on the medical beam of the phasotron of the Joint Institute for Nuclear Research (Dubna). Mice were placed in individual containers and irradiated 4 ones at a time. Irradiation was performed in a modified Bragg peak at doses of 0.5; 1; 2.5 and 5 Gy in caudocranial and craniocaudal direction. Rats were divided into 2 groups: intact control and group irradiated with 170 MeV protons at a dose of 1 Gy, dose rate of 1 Gy / min in the craniocaudal direction. The behavioral responses of experimental animals were tested in the Open Field test on days 1, 7, 14, 30, 90 in rats and on days 8, 30, and 90 in mice. Quantitative analysis of the dilution of Purkinje cells in the rat cerebellum was made, as well as morphological changes in the rat hippocampal neurons. It was shown a development of structural changes after irradiation with protons in neurons of different severity at different times after exposure: after 30 and 90 days. Results: In the period of 1–8 days after proton irradiation of mice and rats in non-lethal doses (0.5–5.0 Gy), there is a dose-independent decrease in the main indicators of the spontaneous locomotor activity of rodents. By the 90th day after irradiation, there is a clear tendency to normalize the indicators of OIR in all groups of irradiated animals, while the ES remains elevated. Disruption of motor activity of rodents irradiated with protons in the early period and its relative normalization in the late post-irradiation period occur on the background of an increased number of morphologically altered and dystrophic neurons in the hippocampus and rarefied of Purkinje cells in the cerebellum. Conclusion: The complex hierarchical structure of the central nervous system, the dependence of its function on the state of the whole organism and its hormonal background, as well as on the state of the blood supply and other factors, along with its high plasticity, require complex physiological, morphological and neurochemical approaches in analyzing the radiobiological effect of corpuscular radiation, taking into consideration the unevenness in dose distribution during irradiation.

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