scholarly journals The metabolism of polyphosphoinositides in hen brain and sciatic nerve

1969 ◽  
Vol 111 (2) ◽  
pp. 157-165 ◽  
Author(s):  
A. Sheltawy ◽  
R. M. C. Dawson
Keyword(s):  
Sciatic Nerve ◽  
Previous Investigation ◽  
Relative Rate ◽  
Specific Radioactivity ◽  
Brain Slices ◽  
Soluble Phosphorus ◽  
Ethanolamine Plasmalogen ◽  
32P Incorporation ◽  
The Brain

1. The distribution of individual phospholipids was determined in hen brain and compared with that in sciatic nerve obtained in a previous investigation. Sciatic nerve is more enriched in the myelinic phospholipids ethanolamine plasmalogen, phosphatidylserine and sphingomyelin, but it contains relatively less triphosphoinositide, and much less diphosphoinositide, than the brain. 2. The course of incorporation of intraperitoneally injected 32P into the acid-soluble phosphorus, phosphoinositides and total phospholipids of hen brain and sciatic nerve was followed. Although the maximum specific radioactivity in sciatic nerve of acid-soluble phosphorus is 4·5 times, and that of triphosphoinositide six times, that in the brain, the relative rate of triphosphoinositide phosphorus synthesis per gram of brain is three times that in sciatic nerve. 3. Administration of the demyelinating agent tri-o-cresyl phosphate to hens has no significant effect on the amounts or the rate of 32P incorporation into the total phospholipids of the sciatic nerve. However, the rate of incorporation of 32P into triphosphoinositide, although not its concentration, is raised from the first day after administration of the drug and remains thus 13 and 23 days later. 4. The incorporation of 32P into polyphosphoinositides of hen brain slices in vitro was studied. The recovery of triphosphoinositide from the slices is markedly increased in the presence of EDTA, although the rate of incorporation of 32P is unaffected. The incorporation of 32P is dependent on the presence of Mg2+ and Ca2+ in the medium, and is decreased when Na+ is replaced with K+ or cholinium ions.

TMOD-31. AN ORGANOTYPIC TISSUE PLATFORM TO BRIDGE IN VITRO AND IN VIVO ASSAYS FOR BRAIN CANCER TREATMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi222-vi222
Author(s):  
Breanna Mann ◽  
Noah Bell ◽  
Denise Dunn ◽  
Scott Floyd ◽  
Shawn Hingtgen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Cancer ◽  
Brain Slice ◽  
Brain Slices ◽  
In Vitro Assays ◽  
Preclinical Model ◽  
Short Period ◽  
The Brain

Abstract Brain cancers remain one of the greatest medical challenges. The lack of experimentally tractable models that recapitulate brain structure/function represents a major impediment. Platforms that enable functional testing in high-fidelity models are urgently needed to accelerate the identification and translation of therapies to improve outcomes for patients suffering from brain cancer. In vitro assays are often too simple and artificial while in vivo studies can be time-intensive and complicated. Our live, organotypic brain slice platform can be used to seed and grow brain cancer cell lines, allowing us to bridge the existing gap in models. These tumors can rapidly establish within the brain slice microenvironment, and morphologic features of the tumor can be seen within a short period of time. The growth, migration, and treatment dynamics of tumors seen on the slices recapitulate what is observed in vivo yet is missed by in vitro models. Additionally, the brain slice platform allows for the dual seeding of different cell lines to simulate characteristics of heterogeneous tumors. Furthermore, live brain slices with embedded tumor can be generated from tumor-bearing mice. This method allows us to quantify tumor burden more effectively and allows for treatment and retreatment of the slices to understand treatment response and resistance that may occur in vivo. This brain slice platform lays the groundwork for a new clinically relevant preclinical model which provides physiologically relevant answers in a short amount of time leading to an acceleration of therapeutic translation.

Effect of Withdrawal from Chronic Ethanol Ingestion on the cAMP Response of Cerebral Cortical Slices Using the Agonists Histamine, Serotonin, and Other Neurotransmitters

1975 ◽  
Vol 53 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Samuel W. French ◽  
Douglas S. Palmer ◽  
Mary E. Narod
Keyword(s):  
Brain Slices ◽  
Ethanol Withdrawal ◽  
Aminobutyric Acid ◽  
Ethanol Ingestion ◽  
Evoked Responses ◽  
Alternative Hypotheses ◽  
Adrenergic Antagonists ◽  
The Brain ◽  
Cortical Slices

The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and γ-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by a- and β-adrenergic antagonists, possibly because of the nonspecific membrane stabilizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.

METABOLISM OF EHRLICH ASCITES TUMOR IN VITRO: SUBCELLULAR DISTRIBUTION OF PHOSPHOLIPIDS NEWLY FORMED FROM14C-LABELED PRECURSORS

1966 ◽  
Vol 44 (11) ◽  
pp. 1461-1468 ◽  
Author(s):  
V. Donisch ◽  
R. J. Rossiter
Keyword(s):  
Microsomal Fraction ◽  
Phosphatidyl Ethanolamine ◽  
Lipid Fraction ◽  
Specific Radioactivity ◽  
Phosphatidyl Inositol ◽  
Phosphatidyl Serine ◽  
Ethanolamine Phosphatidyl ◽  
Ehrlich Ascites ◽  
Ethanolamine Plasmalogen

When Ehrlich ascites cells were incubated in a suitable medium containing choline-1,2-14C, ethanolamine-1,2-14C, L-serine-14C, or glycerol-1-14C, radioactivity was recovered from the lipid fraction. With choline-1,2-14C, radioactivity was incorporated into the three choline-containing phospholipids, lecithin, choline plasmalogen, and sphingomyelin. Radioactivity from ethanolamine-1,2-14C was incorporated into phosphatidyl ethanolamine, ethanolamine plasmalogen, choline plasmalogen, and lecithin. Radioactivity from L-serine-14C was incorporated into phosphatidyl serine, serine plasmalogen, and phosphatide acid, with lesser amounts into phosphatidyl ethanolamine, lecithin, ethanolamine plasmalogen, choline plasmalogen, and sphingomyelin. Radioactivity from glycerol-1-14C was incorporated into the glycerophosphatides, phosphatidic acid, lecithin, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol, and choline plasmalogen. Radioactivity from this precursor was also incorporated into sphingomyelin.In all instances, radioactivity was recovered from the phosphatides in the nuclear, mitochondrial, and microsomal fractions of the tumor. Usually, the specific radioactivity of the phosphatides in the microsomal fraction exceeded that in the other two subcellular fractions.

scholarly journals Cestode larvae excite host neuronal circuits via glutamatergic signaling

2019 ◽  
Author(s):  
Hayley Tomes ◽  
Anja de Lange ◽  
Ulrich Fabien Prodjinotho ◽  
Siddhartha Mahanty ◽  
Katherine Smith ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Imaging Techniques ◽  
Taenia Solium ◽  
Brain Slices ◽  
Receptor Activation ◽  
Excitatory Effect ◽  
Excitatory Neurotransmitter ◽  
Acquired Epilepsy ◽  
The Brain

AbstractNeurocysticercosis (NCC) is caused by the presence of Taenia solium larvae in the brain and is the leading cause of adult-acquired epilepsy worldwide. However, little is known about how seizures emerge in NCC. To address this knowledge gap we used whole-cell patch-clamp electrophysiology and calcium imaging in rodent hippocampal organotypic slice cultures to identify direct effects of cestode larval products on neuronal activity. We found both whole cyst homogenate and excretory/secretory (E/S) products of Taenia larvae have an acute excitatory effect on neurons, which trigger seizure-like events in vitro. Underlying this effect was Taenia-induced neuronal depolarization, which was mediated by glutamate receptor activation but not by nicotinic acetylcholine receptors, acid-sensing ion channels nor Substance P. Glutamate assays revealed the homogenate of both Taenia crassiceps and Taenia solium larvae contained high concentrations of glutamate and that larvae of both species consistently produce and release this excitatory neurotransmitter into their immediate environment. These findings contribute towards the understanding of seizure generation in NCC.Author summaryBrain infection by larvae of the tapeworm Taenia solium (neurocysticercosis or NCC) is the leading cause of acquired epilepsy in adulthood. Little is understood about the mechanisms by which larvae cause seizures. To address this, we used electrophysiological and imaging techniques in rodent brain slices to investigate how tapeworm larvae directly impact neuronal function. We discovered that both the homogenate and secretory products of tapeworm larvae excite neurons and can trigger seizure-like events in brain slices. This effect was caused by the activation of glutamate receptors and not by activating other types of receptors in the brain. Finally, we observed that tapeworm larvae both contain and release the neurotransmitter glutamate into their immediate environment. These findings are relevant for understanding how tapeworm larvae cause seizures in NCC.

Biochemistry

1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Brain Slice ◽  
Brain Slices ◽  
Ringer Solution ◽  
Living Animal ◽  
Dominant Form ◽  
Straight Line ◽  
The Brain

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.

scholarly journals Incorporation of isotopic carbon into cerebral glycogen from non-glucose substrates

1975 ◽  
Vol 146 (1) ◽  
pp. 185-189 ◽  
Author(s):  
M E Phillips ◽  
R V Coxon
Keyword(s):  
Guinea Pig ◽  
Incubation Medium ◽  
Specific Radioactivity ◽  
Brain Slices ◽  
Fresh Tissue ◽  
Radioactive Carbon ◽  
Glucose Carbon ◽  
Pig Brain ◽  
Guinea Pig Brain

1. Measurable incorporation of radioactive carbon from [U-14C]pyruvate, [U-14C]-glutamate and [14C]bicarbonate into the glycogen synthesized by brain slices in vitro was demonstrated. 2. The fructose diphosphatase activity of guinea-pig brain was determined and found to be about 0.03 μmol of substrate degraded/min per g of fresh tissue. 3. The specific radioactivity of the glucose carbon from glycogen relative to that of the precursor added to the incubation medium gave approximate values of 0.195 for glucose, 0.006 for pyruvate, 0.039 for glutamate and 0.001 for bicarbonate.

scholarly journals Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ernesto Flores-Martínez ◽  
Fernando Peña-Ortega
Keyword(s):  
Prefrontal Cortex ◽  
Brain Slices ◽  
Amyloid Β ◽  
Network Activity ◽  
Amyloid Β Peptide ◽  
Cell Level ◽  
Long Range Interactions ◽  
Induced Changes ◽  
The Brain

Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer Disease (AD). Considering that these malfunctions correlate with the increase in the brain’s amyloid beta (Aβ) peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain.

scholarly journals Synergistic Roles of GABAA Receptors and SK Channels in Regulating Thalamocortical Oscillations

2009 ◽  
Vol 102 (1) ◽  
pp. 203-213 ◽  
Author(s):  
Max Kleiman-Weiner ◽  
Mark P. Beenhakker ◽  
William A. Segal ◽  
John R. Huguenard
Keyword(s):  
Brain Slices ◽  
Absence Epilepsy ◽  
Cellular Level ◽  
Reticular Nucleus ◽  
Sk Channels ◽  
Sk Channel ◽  
Spike Wave Discharges ◽  
Thalamocortical Oscillations ◽  
The Brain

Rhythmic oscillations throughout the cortex are observed during physiological and pathological states of the brain. The thalamus generates sleep spindle oscillations and spike-wave discharges characteristic of absence epilepsy. Much has been learned regarding the mechanisms underlying these oscillations from in vitro brain slice preparations. One widely used model to understand the epileptiform oscillations underlying absence epilepsy involves application of bicuculline methiodide (BMI) to brain slices containing the thalamus. BMI is a well-known GABAA receptor blocker that has previously been discovered to also block small-conductance, calcium-activated potassium (SK) channels. Here we report that the robust epileptiform oscillations observed during BMI application rely synergistically on both GABAA receptor and SK channel antagonism. Neither application of picrotoxin, a selective GABAA receptor antagonist, nor application of apamin, a selective SK channel antagonist, alone yielded the highly synchronized, long-lasting oscillations comparable to those observed during BMI application. However, partial blockade of SK channels by subnanomolar concentrations of apamin combined with picrotoxin sufficiently replicated BMI oscillations. We found that, at the cellular level, apamin enhanced the intrinsic excitability of reticular nucleus (RT) neurons but had no effect on relay neurons. This work suggests that regulation of RT excitability by SK channels can influence the excitability of thalamocortical networks and may illuminate possible pharmacological treatments for absence epilepsy. Finally, our results suggest that changes in the intrinsic properties of individual neurons and changes at the circuit level can robustly modulate these oscillations.

scholarly journals Lactate as an oxidizable substrate for rat brain in vitro during the perinatal period

1983 ◽  
Vol 214 (2) ◽  
pp. 633-635 ◽  
Author(s):  
C Arizmendi ◽  
J M Medina
Keyword(s):  
Neonatal Period ◽  
Brain Slices ◽  
High Capacity ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Late Gestation ◽  
Lactate Oxidation ◽  
Energy Substrate ◽  
The Brain

Foetal brain slices showed a high capacity for lactate oxidation in vitro during late gestation. This capacity remained high during the very early postnatal period, suggesting that lactate may play an important role as an energy substrate in the brain during the early neonatal period. The capacity for lactate oxidation decreased markedly during the first 2 days of extra-uterine life and thereafter remained low.

Endogenous oxygen uptake of the hypothalamus in female rats

1964 ◽  
Vol 206 (4) ◽  
pp. 855-857 ◽  
Author(s):  
J. A. Moguilevsky ◽  
M. R. Malinow
Keyword(s):  
Oxygen Uptake ◽  
Brain Slices ◽  
Female Rats ◽  
The Brain

The endogenous oxygen uptake has been determined in the hypothalamus, brain, hypophysis, and uterus of female rats. With the exception of the brain, similar changes have been detected in connection with estrous phases in all of these organs: lower respiratory rates were observed during diestrus and higher ones during estrus. Estradiol and progesterone were added in vitro to hypothalamus and brain slices of estrous and diestrous rats. Although both hormones consistently depressed the Qo2 in brain, such effects were seen only in the hypothalamus of estrous animals.

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