scholarly journals Physiological Responses to Hypoxia in the Absence of Brain Glycogen

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Taylor Zike ◽  
Justin J. Crowder ◽  
Bartholomew A. Pederson
Keyword(s):  
Survival Time ◽  
Motor Coordination ◽  
Glycogen Synthase ◽  
Acute Hypoxia ◽  
Protective Role ◽  
Vaginal Birth ◽  
Sleep Regulation ◽  
Brain Glycogen ◽  
Obstructive Sleep ◽  
The Brain

Background and Hypothesis: Glycogen is a highly branched polymer of glucose and is an important form of energy storage in mammals. The brain is able to form glycogen in astrocytes and neurons via glycogen synthase and branching enzyme. Once formed, brain glycogen functions as the only stored energy source for these cells. Various physiological roles for brain glycogen have been hypothesized, including memory consolidation and sleep regulation, as well as a protective role during various physiological stressors, such as hypoglycemia and hypoxia. For instance, rat brain glycogen levels were decreased 10 minutes after vaginal birth, but not after a C-section. This suggested that cerebral hypoxia experienced during vaginal birth induced the utilization of brain glycogen to minimize neurodegeneration during the hypoxic event. Symptoms of hypoxia can range from tachycardia, tachypnea, shortness of breath, and diaphoresis to confusion, loss of motor coordination and cognitive function, neurodegeneration, and brain death. The many causes of hypoxia include lungs diseases (COPD, pneumonia, pulmonary edema), CNS depressants (opiates), heart problems (CHF), anemia, and obstructive sleep apnea (OSA). We hypothesized that the lack of brain glycogen would cause a noticeable detrimental effect to the survival time and physiologic functions of mice exposed to acute hypoxia. Experimental Design or Project Methods: We subjected mice, with or without glycogen synthase disrupted in the brain, to carbon dioxide- or nitrogen-induced hypoxia and monitored effects on brain glycogen levels, behavior, and survival time. Results: We found that mice lacking brain glycogen exhibited the characteristic physiologic responses to hypoxia, but expired ~50% sooner than mice with brain glycogen. Conclusion and Potential Impact: These results provide evidence that brain glycogen is imperative in responding to hypoxic events. Further, these findings suggest that brain glycogen may protect patients with OSA against other comorbidities, especially neurodegeneration and cognitive impairment.

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

2020 ◽  
Vol 26 (21) ◽  
pp. 2492-2496 ◽  
Author(s):  
Fiammetta Romano ◽  
Giovanna Muscogiuri ◽  
Elea Di Benedetto ◽  
Volha V. Zhukouskaya ◽  
Luigi Barrea ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sleep Disorders ◽  
Vitamin D Deficiency ◽  
Sleep Apnea Syndrome ◽  
Regulatory Mechanisms ◽  
Sleep Regulation ◽  
Vitamin D Receptors ◽  
Obstructive Sleep ◽  
The Impact

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. Conclusions: : Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

scholarly journals Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

2021 ◽  
Vol 22 (2) ◽  
pp. 759
Author(s):  
Karen P. Briski ◽  
Mostafa M. H. Ibrahim ◽  
A. S. M. Hasan Mahmood ◽  
Ayed A. Alshamrani
Keyword(s):  
Alternative Energy ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Receptor Expression ◽  
Hypothalamic Nucleus ◽  
Control Structures ◽  
Ventromedial Hypothalamic Nucleus ◽  
Glycogen Reserve ◽  
Noradrenergic Modulation ◽  
The Brain

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR). The current review discusses recent affirmative evidence that neuro-metabolic stability in the VMN may be shaped by NE influence on astrocyte glycogen metabolism and glycogen-derived substrate fuel supply. Noradrenergic modulation of estrogen receptor (ER) control of VMN glycogen phosphorylase (GP) isoform expression supports the interaction of catecholamine and estradiol signals in shaping the physiological stimulus-specific control of astrocyte glycogen mobilization. Sex-dimorphic NE control of glycogen synthase and GP brain versus muscle type proteins may be due, in part, to the dissimilar noradrenergic governance of astrocyte AR and ER variant profiles in males versus females. Forthcoming advances in the understanding of the molecular mechanistic framework for catecholamine stimulus integration with other regulatory inputs to VMN astrocytes will undoubtedly reveal useful new molecular targets in each sex for glycogen mediated defense of neuronal metabolic equilibrium during neuro-glucopenia.

scholarly journals Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2669
Author(s):  
Reiner Wiest ◽  
Thomas S. Weiss ◽  
Lusine Danielyan ◽  
Christa Buechler
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Clearance ◽  
Protective Role ◽  
Tissue Growth ◽  
Cirrhotic Liver ◽  
Diabetic Patients ◽  
Peripheral Clearance ◽  
End Stage ◽  
The Brain

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child–Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = −0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction.

scholarly journals Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 3829
Author(s):  
Mohamed F. Dora ◽  
Nabil M. Taha ◽  
Mohamed A. Lebda ◽  
Aml E. Hashem ◽  
Mohamed S. Elfeky ◽  
...  
Keyword(s):  
Iron Oxide ◽  
B Cell Lymphoma ◽  
Basal Diet ◽  
Protective Role ◽  
Iron Oxide Nanoparticle ◽  
Albino Rats ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Brain

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

827 Central Sleep Apnea in a patient with Multiple Sclerosis

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A322-A323
Author(s):  
Rahul Dasgupta ◽  
Sonja Schütz ◽  
Tiffany Braley
Keyword(s):  
Multiple Sclerosis ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disordered Breathing ◽  
Central Sleep Apnea ◽  
Progressive Multiple Sclerosis ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Demyelinating Lesions ◽  
The Brain

Abstract Introduction Sleep-disordered breathing is common in persons with multiple sclerosis (PwMS), and may contribute to debilitating fatigue and other chronic MS symptoms. The majority of research to date on SDB in MS has focused on the prevalence and consequences of obstructive sleep apnea; however, PwMS may also be at increased risk for central sleep apnea (CSA), and the utility of methods to assess CSA in PwMS warrant further exploration. We present a patient with secondary progressive multiple sclerosis who was found to have severe central sleep apnea on WatchPAT testing. Report of case(s) A 61 year-old female with a past medical history of secondary progressive multiple sclerosis presented with complaints of fragmented sleep. MRI of the brain, cervical spine, and thoracic spine showed numerous demyelinating lesions in the brain, brainstem, cervical, and thoracic spinal cord. Upon presentation, the patient noted snoring, witnessed apneas, and daytime sleepiness. WatchPAT demonstrated severe sleep apnea, with a pAHI of 63.3, and a minimum oxygen saturation of 90%. The majority of the scored events were non-obstructive in nature (73.1% of all scored events), and occurred intermittently in a periodic fashion. Conclusion The differential diagnosis of fatigue in PwMS should include sleep-disordered breathing, including both obstructive and central forms of sleep apnea. Demyelinating lesions in the brainstem (which may contribute to impairment of motor and sensory networks that control airway patency and respiratory drive), and progressive forms of MS, have been linked to both OSA and CSA. The present data illustrate this relationship in a person with progressive MS, and offer support for the WatchPAT as a cost-effective means to evaluate for both OSA and CSA in PwMS, while reducing patient burden. PwMS may be at increased risk for CSA. Careful clinical consideration should be given to ordering appropriate sleep testing to differentiate central from obstructive sleep apnea in PwMS, particularly for patients with demyelinating lesions in the brainstem. Support (if any) 1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014 Feb 15;10(2):155–62. doi: 10.5664/jcsm.3442. PMID: 24532998; PMCID: PMC3899317.

Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov
Keyword(s):  
Acute Hypoxia ◽  
Life Time ◽  
The Body ◽  
Cerebral Hemispheres ◽  
Antihypoxic Activity ◽  
Hypoxic Episode ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Outbred Mice ◽  
The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

scholarly journals The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173175 ◽  
Author(s):  
Kanehiro Hayashi ◽  
Asako Furuya ◽  
Yuriko Sakamaki ◽  
Takumi Akagi ◽  
Yo Shinoda ◽  
...  
Keyword(s):  
Dendritic Growth ◽  
Motor Coordination ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule ◽  
The Brain
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