Glycogen: Multiple Roles in the CNS

2016 ◽  
Vol 23 (4) ◽  
pp. 356-363 ◽  
Author(s):  
Laura Rich ◽  
Angus M. Brown
Keyword(s):  
Glycogen Metabolism ◽  
Prenatal Development ◽  
Brain Parenchyma ◽  
Multiple Roles ◽  
Primary Role ◽  
Neuronal Function ◽  
Brain Functions ◽  
Continuous Support ◽  
The Brain

The historically neurocentric view of astrocytes as Styrofoam cushioning that rigidly clad neurons within the brain parenchyma has been superseded in the past 30 years by an increasing appreciation of the myriad roles astrocytes contribute to supporting physiological brain function. It is widely recognized that the continuous support provided by astrocytes, from prenatal development to maturity, is vital for neuronal function. Indeed, the numerous and diverse roles furnished by astrocytes contrasts with the vital but restricted transmission of action potentials that is the neuron’s primary role. An emerging role for astrocytes is that of providing energy substrate in the form of glycogen-derived lactate to neurons. This role was established during periods of limited glucose availability but has been extended to encompass one of the most important physiological brain functions, learning and memory. In this context glycogen metabolism is integral to the consolidation of learning into long-term retention of memories, a process vital to the higher functioning of the human brain.

scholarly journals Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Expression Patterns ◽  
Brain Parenchyma ◽  
Primary Role ◽  
And Function ◽  
Inflammatory Milieu ◽  
The Brain ◽  
Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

scholarly journals GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1683
Author(s):  
Octavio Silva-García ◽  
Ricarda Cortés-Vieyra ◽  
Francisco N. Mendoza-Ambrosio ◽  
Guillermo Ramírez-Galicia ◽  
Víctor M. Baizabal-Aguirre
Keyword(s):  
Neurodegenerative Disorders ◽  
Glycogen Synthase ◽  
Similar Efficacy ◽  
Glycogen Synthase Kinase 3 ◽  
Brain Functions ◽  
Chemical Inhibitors ◽  
Simultaneous Inhibition ◽  
The Brain

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders (ND) and cancer. Although various chemical inhibitors of these enzymes restore the brain functions in models of ND such as Alzheimer’s disease (AD), and reduce the proliferation and survival of cancer cells, the particular contribution of each paralog to these effects remains unclear as these molecules downregulate the activity of both paralogs with a similar efficacy. Moreover, given that GSK3 paralogs phosphorylate more than 100 substrates, the simultaneous inhibition of both enzymes has detrimental effects during long-term inhibition. Although the GSK3β kinase function has usually been taken as the global GSK3 activity, in the last few years, a growing interest in the study of GSK3α has emerged because several studies have recognized it as the main GSK3 paralog involved in a variety of diseases. This review summarizes the current biological evidence on the role of GSK3α in AD and various types of cancer. We also provide a discussion on some strategies that may lead to the design of the paralog-specific inhibition of GSK3α.

scholarly journals Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

2018 ◽  
Vol 73 (Suppl. 5) ◽  
pp. 43-52 ◽  
Author(s):  
John D. Fernstrom
Keyword(s):  
Monosodium Glutamate ◽  
Safety Evaluation ◽  
The Body ◽  
Neuronal Function ◽  
Excitatory Neurotransmitter ◽  
Brain Functions ◽  
The Central Nervous System ◽  
Experimental Findings ◽  
The Brain ◽  
Amino Acid Glutamate

The non-essential amino acid glutamate participates in numerous metabolic pathways in the body. It also performs important physiologic functions, which include a sensory role as one of the basic tastes (as monosodium glutamate [MSG]), and a role in neuronal function as the dominant excitatory neurotransmitter in the central nervous system. Its pleasant taste (as MSG) has led to its inclusion as a flavoring agent in foods for centuries. Glutamate’s neurotransmitter role was discovered only in the last 60 years. Its inclusion in foods has necessitated its safety evaluation, which has raised concerns about its transfer into the blood ultimately increasing brain glutamate levels, thereby causing functional disruptions because it is a neurotransmitter. This concern, originally raised almost 50 years ago, has led to an extensive series of scientific studies to examine this issue, conducted primarily in rodents, non-human primates, and humans. The key findings have been that (a) the ingestion of MSG in the diet does not produce appreciable increases in glutamate concentrations in blood, except when given experimentally in amounts vastly in excess of normal intake levels; and (b) the blood-brain barrier effectively restricts the passage of glutamate from the blood into the brain, such that brain glutamate levels only rise when blood glutamate concentrations are raised experimentally via non-physiologic means. These and related discoveries explain why the ingestion of MSG in the diet does not lead to an increase in brain glutamate concentrations, and thus does not produce functional disruptions in brain. This article briefly summarizes key experimental findings that evaluate whether MSG in the diet poses a threat to brain function.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals Neurobehavioral effects of choninergic drugs in prenatal period

2017 ◽  
Vol 15 (3) ◽  
pp. 5-21 ◽  
Author(s):  
Elena V. Stashina ◽  
Nikolay A. Gavrilov ◽  
Petr D. Shabanov
Keyword(s):  
Reproductive Function ◽  
Prenatal Development ◽  
Environmental Toxicants ◽  
Critical Periods ◽  
Brain Neurotransmitter ◽  
Neurobehavioral Deficits ◽  
Neurobehavioral Effects ◽  
The Brain ◽  
Prenatal Effects

Environmental toxicants, chemicals exhibiting with cholinotropics properties, and drugs – agonists and antagonists of M- and N-cholinergic receptors by acting on the developing brain of the fetus in the embryonic period of ontogenesis, cause a change the activity of the cholinergic mechanisms of the brain during critical periods of prenatal development with the subsequent disruption of the formation of different brain systems, primarily the ontogeny of nerve cells and brain neurotransmitter systems. These changes in the long term is correlated with neurobehavioral deficits from adult individuals, dysfunction of the reproductive system of adult offspring. The relevance of the study of prenatal effects of cholinergic factors on the central mechanisms of reproductive function, memory processes and learning during ontogenetic development of the organism due to the need of prevention and treatment of subsequent mental, behavioral, and sexual dysfunctions, and abnormal sexual behavior, infertility.

Treatment Model of CNS Lymphoma Using Complement-Dependent Cytotoxicity Induced by Rituximab and Autoserum.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3739-3739
Author(s):  
Yasuyuki Miyake ◽  
Yasushi Okoshi ◽  
Takayuki Machino ◽  
Shigeru Chiba
Keyword(s):  
Lateral Ventricle ◽  
Raji Cell ◽  
Technical Problem ◽  
Brain Parenchyma ◽  
Autologous Serum ◽  
Ependymal Cells ◽  
Treatment Model ◽  
Complement Dependent Cytotoxicity ◽  
The Brain

Abstract Abstract 3739 Poster Board III-675 Background Primary central nervous system lymphoma (PCNSL) is almost exclusively CD20-positive non-Hodgkin lymphoma (NHL). Although rituximab (R) is widely used for CD20-positive NHL, it is not considered to reach brain lesions effectively beyond the blood brain barrier. Intraventricule administration (ivt) of R is reported to be effective in meningeal lymphoma but the effect on lesions in the brain parenchyma seems to be limited. Recently, a case of refractory PCNSL that was successfully treated with ivt of R with autologous serum was reported (Takami A, et al. Cancer Science, 2006). Because the cerebrospinal fluid does not contain complements which exists in the serum, induction of complement-dependent cytotoxicity by ivt of R plus autoserum was speculated. To investigate this effect, we developed an animal treatment model of CNSL. Materials and methods Raji, CD20-positive Burkitt lymphoma cell line, was inoculated into the deep frontal lobe of the brain of 8-week old F344 (nru-/nru-) nude rats, using brain stereotaxic apparatus. At the same time, a cannula was placed into the ipsilateral lateral ventricle. After several days, R or control immunoglobulin (cIg), plus human serum or saline, was administrated into the lateral ventricle. Results The brain was extracted 24 hours after the last administration and frozen section was made. Human CD20-positive Raji cell tumor was also positively stained with FITC-conjugated anti-human IgG antibody when R but not cIg was administrated. Consequently, R in the lateral ventricle was considered to penetrate ependymal cells and brain parenchyma, and bound to lymphoma cells. Next, these rats were treated with ivt of R plus serum (R + Serum), cIg plus serum (cIg + Serum), or R plus saline (R + saline). These were administrated once a day from day 5 to day 9 after inoculation of Raji, and then survival was monitored. When an obvious weakness, such as marked and consecutively loss of activity or weight, was observed, these rats were euthanized and this is defined as dead day. In each case, the brain was extirpated and examined whether lymphoma existed or not. Death without lymphoma or from technical problem was excluded from the analysis. Survival of each group was analyzed by Kaplan-Meier method and log-lank test. R + Serum group had longer survival than cIg + Serum (p = 0.049). Long-term survivors were only seen in R + Serum and this group seemed to be superior to R + saline but statistical difference was not detected (p = 0.083). There were no difference between cIg + Serum and R + saline (p =0.382) and neither group had long-term survivor. Conclusion The possibility of novel treatment of CNSL with ivt of R and autoserum was shown in the rat CNSL model. To confirm this approach, clinical trials are warranted. Disclosures: No relevant conflicts of interest to declare.

‘Alzheimer-like’ pathology in a murine model of arterial hypertension

2011 ◽  
Vol 39 (4) ◽  
pp. 939-944 ◽  
Author(s):  
Daniela Carnevale ◽  
Giuseppe Lembo
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Strong Association ◽  
Epidemiological Studies ◽  
Brain Parenchyma ◽  
Murine Models ◽  
Ad Alzheimer’S Disease ◽  
The Brain

Genetic AD (Alzheimer's disease) accounts for only few AD cases and is almost exclusively associated with increased amyloid production in the brain. Instead, most patients are affected with the sporadic form of AD and typically have altered clearance mechanisms. The identification of factors that influence the onset and progression of sporadic AD is a key step towards understanding its mechanism(s) and developing successful therapies. An increasing number of epidemiological studies describe a strong association between AD and cardiovascular risk factors, particularly hypertension, that exerts detrimental effects on the cerebral circulation, favouring chronic brain hypoperfusion. However, a clear demonstration of a pathophysiological link between cardiovascular risk factors and AD aetiology is still missing. To increase our knowledge of the mechanisms involved in the brain's response to hypertension and their possible role in promoting amyloid deposition in the brain, we have performed and investigated in depth different murine models of hypertension, induced either pharmacologically or mechanically, leading in the long term to plaque formation in the brain parenchyma and around blood vessels. In the present paper, we review the major findings in this particular experimental setting that allow us to study the pathogenetic mechanisms of sporadic AD triggered by vascular risk factors.

scholarly journals Effects of long-term and brain-wide colonization of peripheral bone-marrow derived myeloid cells in the CNS

2020 ◽  
Author(s):  
Lindsay A. Hohsfield ◽  
Allison R. Najafi ◽  
Yasamine Ghorbanian ◽  
Neelakshi Soni ◽  
Edna E. Hingco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Cells ◽  
Marrow Transplant ◽  
Brain Parenchyma ◽  
Immune Defense ◽  
Whole Body ◽  
Long Term Effects ◽  
The Brain ◽  
Peripheral Bone

Abstract Background Microglia, the primary resident myeloid cells of brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfunction has been implicated in a number of central nervous system (CNS) disorders, thus developing tools to manipulate and replace these myeloid cells in CNS is of therapeutic interest. Methods Using whole body irradiation, bone marrow transplant, and colony-stimulating factor 1 receptor inhibition, we achieve long-term and brain-wide (~ 80%) engraftment and colonization of peripheral bone marrow-derived myeloid cells (i.e. monocytes) in the brain parenchyma and evaluated the long-term effects of their colonization in the CNS. Results Here, we identify a monocyte signature that includes an upregulation in Ccr1, Ms4a6b, Ms4a6c, Ms4a7, Apobec1, Lyz2, Mrc1, Tmem221, Tlr8, Lilrb4a, Msr1, Nnt, and Wdfy1, and a downregulation of Siglech, Slc2a5, and Ccl21a/b. We demonstrate that irradiation and long-term (~ 6 months) engraftment of the CNS by monocytes induces brain-region dependent alterations in transcription profiles, astrocytes, neuronal structures, including synaptic components, and cognition. Although our results show that microglial replacement with peripheral derived myeloid cells is feasible and that irradiation-induced changes can be reversed by the replacement of microglia with monocytes in the hippocampus, we also observe that brain-wide engraftment of peripheral myeloid cells (relying on irradiation) can result in cognitive and synaptic deficits. Conclusions These findings provide insight into better understanding the role and complexity of myeloid cells in the brain, including their regulation of other CNS cells and functional outcomes.

scholarly journals Impairment in Long-Term Memory Formation and Learning-Dependent Synaptic Plasticity in Mice Lacking Glycogen Synthase in the Brain

2013 ◽  
Vol 33 (4) ◽  
pp. 550-556 ◽  
Author(s):  
Jordi Duran ◽  
Isabel Saez ◽  
Agnes Gruart ◽  
Joan J Guinovart ◽  
José M Delgado-García
Keyword(s):  
Cognitive Abilities ◽  
Glycogen Synthase ◽  
Long Term Potentiation ◽  
Normal Activity ◽  
Synaptic Strength ◽  
Long Term Memory ◽  
Brain Functions ◽  
The Brain

Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength.

scholarly journals Mapping of Brain Functions and Spatial Luminance Distributions as Innovative Tools for Assessing Discomfort Glare in the Built Environment

2007 ◽  
Vol 4 (1) ◽  
Author(s):  
Peter Raynham ◽  
Werner Osterhaus ◽  
Michael Davies
Keyword(s):  
Built Environment ◽  
Proof Of Concept ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Brain Functions ◽  
Discomfort Glare ◽  
Innovative Tool ◽  
New Research ◽  
The Brain

A series of "proof-of-concept" projects are set out aimed at bringing together built environment researchers attempting to understand what constitutes ‘comfortable’ space and neuroscientists investigating the functional characteristics of the human brain. The long-term goal is to address the question of whether there are regions of the brain that are specifically engaged when people experience spaces they consider to be comfortable, pleasing or even beautiful. Glare is an area of research that has been recognised as a problem in both interior and exterior lighting. Recent advances in technology make it an ideal candidate for the proposed “proof-of-concept” study. The mapping of brain functions through functional magnetic resonance imaging, the mapping of luminance distributionsin a visual scene, and the study of distraction and its influence on discomfort glare can be combined to form the basis of an innovative tool box for new research.

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