scholarly journals Glycogen as a Putative Target for Diagnosis and Therapy in Brain Pathologies

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jean-François Cloix ◽  
Tobias Hévor
Keyword(s):  
Chronic Conditions ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Therapeutic Approaches ◽  
Brain Glycogen ◽  
Putative Target ◽  
Glucose Polymer ◽  
Energy Store ◽  
High Level ◽  
The Brain

Brain glycogen, a glucose polymer, is now considered as a functional energy store to the brain. Indeed, when neurons outpace their own possibilities to provide themselves with energy, astrocytic metabolism is in charge of feeding neurons, since brain glycogen synthesis is mainly due to astrocyte. Therefore, malfunctions or perturbations of astrocytic glycogen content, synthesis, or mobilization may be involved in processes of brain pathologies. This is the case, for example, in epilepsies and gliomas, two different situations in which, brain needs high level of energy during acute or chronic conditions. The purpose of the present paper is to demonstrate how brain glycogen might be relevant in these two pathologies and to pinpoint the possibilities of considering glycogen as a tool for diagnostic and therapeutic approaches in brain pathologies.

Seasonal changes in glycogen content and Na+-K+-ATPase activity in the brain of crucian carp

2006 ◽  
Vol 291 (5) ◽  
pp. R1482-R1489 ◽  
Author(s):  
Matti Vornanen ◽  
Vesa Paajanen
Keyword(s):  
Atpase Activity ◽  
Seasonal Changes ◽  
Crucian Carp ◽  
Glycogen Content ◽  
Hill Coefficient ◽  
Ouabain Binding ◽  
Brain Glycogen ◽  
Na Pump ◽  
Glycogen Stores ◽  
The Brain

Changes in the number of Na+-K+-ATPase α-subunits, Na+-K+-ATPase activity and glycogen content of the crucian carp ( Carassius carassius) brain were examined to elucidate relative roles of energy demand and supply in adaptation to seasonal anoxia. Fish were collected monthly around the year from the wild for immediate laboratory assays. Equilibrium dissociation constant and Hill coefficient of [3H]ouabain binding to brain homogenates were 12.87 ± 2.86 nM and −1.18 ± 0.07 in June and 11.93 ± 2.81 nM and −1.17 ± 0.06 in February ( P > 0.05), respectively, suggesting little changes in Na+-K+-ATPase α-subunit composition of the brain between summer and winter. The number of [3H]ouabain binding sites and Na-K-ATPase activity varied seasonally ( P < 0.001) but did not show clear connection to seasonal changes in oxygen content of the fish habitat. Six weeks’ exposure of fish to anoxia in the laboratory did not affect Na+-K+-ATPase activity ( P > 0.05) confirming the anoxia resistance of the carp brain Na pump. Although anoxia did not suppress the Na pump, direct Q10 effect on Na+-K+-ATPase at low temperatures resulted in 10 times lower catalytic activity in winter than in summer. Brain glycogen content showed clear seasonal cycling with the peak value of 203.7 ± 16.1 μM/g in February and a 15 times lower minimum (12.9 ± 1.2) in July. In winter glycogen stores are 15 times larger and ATP requirements of Na+-K+-ATPase at least 10 times less than in summer. Accordingly, brain glycogen stores are sufficient to fuel brain function for about 8 min in summer and 16 h in winter, meaning about 150-fold extension of brain anoxia tolerance by seasonal changes in energy supply-demand ratio.

Conversion of glucose to glycogen after ingestion of a high-carbohydrate diet

1960 ◽  
Vol 198 (4) ◽  
pp. 787-792 ◽  
Author(s):  
A. Chari-Bitron ◽  
S. Lepkovsky ◽  
R. M. Lemmon ◽  
M. K. Dimick
Keyword(s):  
Muscle Glycogen ◽  
Glycogen Content ◽  
Intermediate Compound ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
Experimental Conditions ◽  
Brain Glycogen ◽  
High Carbohydrate ◽  
The Brain

The glycogen content of nine tissues of trained-fed rats was investigated at fasting and at different times after eating with and without water. With the exception of the brain and muscles, the tissues contained little or no glycogen at fasting and accumulated variable amounts during the course of digestion with peak accumulation in most cases 4–7 hours after the commencement of feeding. The brain glycogen did not vary in the rats in spite of the different experimental conditions of this study. The amount of muscle glycogen in the fed rats was the same or slightly more than the amount found in the fasting rats. The fasting liver incorporated C14 substrates into glycogen while it was decreasing in amounts. Fasting muscles incorporated C14 substrates almost as fast as fed muscles indicating that muscle glycogen behaved as an intermediate compound and was metabolized as fast as formed. Accumulation of glycogen in the mesenteric, renal and subcutaneous fatty tissues was decreased by a) feeding without water and b) excessive deposits of fat in the fatty tissues.

scholarly journals Understanding the development of amblyopia using macaque monkey models

2019 ◽  
Vol 116 (52) ◽  
pp. 26217-26223 ◽  
Author(s):  
Lynne Kiorpes
Keyword(s):  
Macaque Monkey ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
History Of ◽  
Visual Motor ◽  
Perceptual Abilities ◽  
High Level ◽  
And Function ◽  
The Brain ◽  
Insight Into

Amblyopia is a sensory developmental disorder affecting as many as 4% of children around the world. While clinically identified as a reduction in visual acuity and disrupted binocular function, amblyopia affects many low- and high-level perceptual abilities. Research with nonhuman primate models has provided much needed insight into the natural history of amblyopia, its origins and sensitive periods, and the brain mechanisms that underly this disorder. Amblyopia results from abnormal binocular visual experience and impacts the structure and function of the visual pathways beginning at the level of the primary visual cortex (V1). However, there are multiple instances of abnormalities in areas beyond V1 that are not simply inherited from earlier stages of processing. The full constellation of deficits must be taken into consideration in order to understand the broad impact of amblyopia on visual and visual–motor function. The data generated from studies of animal models of the most common forms of amblyopia have provided indispensable insight into the disorder, which has significantly impacted clinical practice. It is expected that this translational impact will continue as ongoing research into the neural correlates of amblyopia provides guidance for novel therapeutic approaches.

Central Nervous Function and Changes in Brain Metabolite Concentration

1953 ◽  
Vol 30 (4) ◽  
pp. 468-475
Author(s):  
M. R. A. CHANCE
Keyword(s):  
Glycogen Content ◽  
Brain Activity ◽  
Defensive Behaviour ◽  
Normal Behaviour ◽  
External Stimulation ◽  
Brain Glycogen ◽  
Brain Metabolite ◽  
Nervous Function ◽  
The Brain ◽  
Different Parts

1. The changes in the glycogen content of different parts of the brain have been studied in mice in relation to the behaviour of these animals. 2. Increases in glycogen content have been demonstrated after a jump, a fall, after the righting reaction accompanying a fall, and after aggressive behaviour has been shown in a fight. 3. No increase has been demonstrated during sleep, after running or walking, or after defensive behaviour in a fight. 4. It was shown earlier that external stimulation must reach convulsive intensity to produce an increase in brain glycogen, and it is suggested that the particular forms of normal behaviour associated with increase in brain glycogen involve a ‘convulsive’ type of brain activity. ‘Convulsive’ in this context may mean either a disturbance of the metabolism in some or all of the brain cells, or alternatively the mobilization of cell populations for simultaneous, and probably rapid, discharge. At present there is no evidence to suggest whether either or both of these possibilities are involved.

Lessons From the Neural Bases of Speech and Voice

2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow
Keyword(s):  
Brain Networks ◽  
Neural Substrates ◽  
Voice Behavior ◽  
Therapeutic Approaches ◽  
Neural Bases ◽  
Sound Foundation ◽  
The Brain ◽  
Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

ÉTUDE IN VITRO DU MÉTABOLISME DES HYDRATES DE CARBONE DANS LE LEUCOCYTE CIRCULANT DU COBAYE TRAITÉ À LA CORTISONE

1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti
Keyword(s):  
Glucose Concentration ◽  
Intramuscular Injection ◽  
Acute Inflammation ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
List Type ◽  
Hydrates De Carbone

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood

2020 ◽  
Vol 51 (05) ◽  
pp. 336-340 ◽  
Author(s):  
Fatma Hanci ◽  
Sevim Türay ◽  
Paşa Balci ◽  
Nimet Kabakuş
Keyword(s):  
Seizure Control ◽  
Hot Water ◽  
Reflex Epilepsy ◽  
Therapeutic Approaches ◽  
Water Age ◽  
Epileptiform Discharges ◽  
Neurology Clinic ◽  
Neuromuscular Development ◽  
The Brain ◽  
International League

AbstractHot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

scholarly journals Metabolism in the Zebrafish Retina

2021 ◽  
Vol 9 (1) ◽  
pp. 10
Author(s):  
Natalia Jaroszynska ◽  
Philippa Harding ◽  
Mariya Moosajee
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Therapeutic Approaches ◽  
Retinal Photoreceptors ◽  
Sufficient Energy ◽  
Metabolic Products ◽  
Sight Loss ◽  
Choroidal Vasculature ◽  
The Brain

Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches.

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. E28-E35 ◽  
Author(s):  
Michale Bouskila ◽  
Michael F. Hirshman ◽  
Jørgen Jensen ◽  
Laurie J. Goodyear ◽  
Kei Sakamoto
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Wild Type ◽  
Muscle Glycogen Synthesis ◽  
Mutant Forms

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6- P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3α and -β genes are replaced with mutant forms (GSK3α/βS21A/S21A/S9A/S9A), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3α/βS21A/S21A/S9A/S9Amice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6- P, the rate of [14C]glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[3H]glucose and [14C]glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6- P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo.

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