scholarly journals Fatty Acids in Energy Metabolism of the Central Nervous System

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Alexander Panov ◽  
Zulfiya Orynbayeva ◽  
Valentin Vavilin ◽  
Vyacheslav Lyakhovich
Keyword(s):  
Fatty Acids ◽  
Energy Metabolism ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Metabolic Phenotype ◽  
Neuronal Excitation ◽  
Palmitoyl Carnitine ◽  
The Central Nervous System ◽  
Mitochondrial Oxidation ◽  
The Brain

In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain’s energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcileβ-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

scholarly journals Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde
Keyword(s):  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Lipid Transport ◽  
Omega 3 ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

scholarly journals Identification of the SNARE complex mediating the exocytosis of NMDA receptors

2016 ◽  
Vol 113 (43) ◽  
pp. 12280-12285 ◽  
Author(s):  
Yi Gu ◽  
Richard L. Huganir
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Total Internal Reflection ◽  
De Novo ◽  
Receptor Trafficking ◽  
Snare Complex ◽  
Synaptic Membranes ◽  
Rab Proteins ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system, NMDA receptors mediate excitatory neurotransmissions and play important roles in synaptic plasticity. The regulation of NMDA receptor trafficking is critical for neural functions in the brain. Here, we directly visualized individual exocytic events of NMDA receptors in rat hippocampal neurons by total internal reflection fluorescence microscopy (TIRFM). We found that the constitutive exocytosis of NMDA receptors included both de novo exocytic and recycling events, which were regulated by different Rab proteins. We also identified the SNAP25–VAMP1–syntaxin4 complex mediating the constitutive exocytosis of NMDA receptors. Transient knockdown of each component of the SNARE complex interfered with surface delivery of NMDA receptors to both extrasynaptic and synaptic membranes. Our study uncovers the postsynaptic function of the SNAP25–VAMP1–syntaxin4 complex in mediating the constitutive exocytosis of NMDA receptors, suggesting that this SNARE complex is involved in excitatory synaptic transmission.

scholarly journals Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD+ Concentration in Human Primary Astrocytes

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4779 ◽  
Author(s):  
Ross Grant ◽  
Susan Nguyen ◽  
Gilles Guillemin
Keyword(s):  
Nicotinic Acid ◽  
De Novo ◽  
Culture Media ◽  
Kynurenine Pathway ◽  
The Body ◽  
Tryptophan Degradation ◽  
Major Cell Type ◽  
The Central Nervous System ◽  
The Relationship ◽  
The Brain

Efficient synthesis of NAD+ is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD+. The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD+ synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD+ levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD+ levels after 24 hrs. This decrease in NAD+ was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide.

scholarly journals Omega – 3 fatty acids in schizophrenia – part I: importance in the pathophysiology of schizophrenia

2016 ◽  
Vol 17 (3) ◽  
pp. 198-213
Author(s):  
Joanna Róg ◽  
Hanna Karakuła-Juchnowicz
Keyword(s):  
Fatty Acids ◽  
Nervous System ◽  
Essential Fatty Acids ◽  
Dry Weight ◽  
Omega 3 ◽  
Metabolic Complications ◽  
The Central Nervous System ◽  
David Horrobin ◽  
The Brain

AbstractDespite the increasing offer of antipsychotic drugs, the effectiveness of pharmacotherapy in schizophrenia is still unsatisfactory. Drug resistance, lack of complete remission and the increasing risk of metabolic complications are the reasons why the new forms of therapy in schizophrenia among which unsaturated essential fatty acids omega 3 (EFAs ω-3) affecting the proper functioning of nervous system, are mentioned, are being looked for.Fatty acids represent 50-60% of the dry weight of the brain and diet is one of the factors that influence the value of each of the fat fractions in the neuron membranes. Patients with schizophrenia tend to have irregular nutritional status concerning essential fatty acids ω-3, which might result from metabolic disorders or irregular consumption of fatty acids.Apart from being a review of the literature on this subject, this very paper characterizes essential fatty acids ω-3, their metabolism, the most important sources in the diet and the opinions of experts in the field about the recommended intake. It pays attention to the role of essential fatty acids in both the structure and functioning of the central nervous system is, as well as their role in the pathophysiology of schizophrenia, with particular emphasis on the membrane concept by David Horrobin. The assessment of the errors in consumption and metabolism of essential fatty acids are described as well.The evidence was found both in epidemiological and modeling studies. It supports the participation of EFAs in etiopathogenesis and pathophysiology of schizophrenia. Further research is needed, both observational and interventional, as to the role of essential fatty acids ω-3 in the functioning of the CNS as well as the development and course of schizophrenia.

scholarly journals FATTY ACIDS AND ALZHEIMER’S DISEASE: EVIDENCE ON COGNITION AND CORTICAL ?-AMYLOID FROM SECONDARY ANALYSES OF THE MULTIDOMAIN ALZHEIMER PREVENTIVE TRIAL

2018 ◽  
pp. 1-3
Author(s):  
C. Hooper ◽  
B. Vellas
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Monounsaturated Fatty Acids ◽  
Omega 3 ◽  
Trans Fats ◽  
Omega 6 ◽  
Inflammatory Processes ◽  
Secondary Analyses ◽  
And Function ◽  
The Brain

Fatty acids are long-chain hydrocarbons that can be separated into four groups: saturated, monounsaturated, polyunsaturated, and trans fats (1). The brain is highly enriched in fatty acids particularly polyunsaturated fatty acids (PUFAs) with docosahexaenoic acid (an omega 3: n-3 PUFA) and arachidonic acid (an omega 6: n-6 PUFA) being the most abundant (2,3). Fats control the structure and function of cell membranes and therefore impact upon signal transduction and neurotransmission and PUFAs play a role in inflammatory processes (4). Saturated and monounsaturated fatty acids can be synthesized de novo within the brain, but PUFAs are mainly supplied by the blood (5).

scholarly journals N-3 fatty acids, neuronal activity and energy metabolism in the brain

2012 ◽  
Vol 19 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Emilie Harbeby ◽  
Fabien Pifferi ◽  
Mélanie Jouin ◽  
Hélène Pélerin ◽  
Sébastien Tremblay ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Energy Metabolism ◽  
Neuronal Activity ◽  
The Brain

Lipid metabolism in skeletal muscle: generation of adaptive and maladaptive intracellular signals for cellular function

2012 ◽  
Vol 302 (11) ◽  
pp. E1315-E1328 ◽  
Author(s):  
Matthew J. Watt ◽  
Andrew J. Hoy
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Muscle Physiology ◽  
Triacylglycerol Metabolism ◽  
Intracellular Signals ◽  
Recent Developments ◽  
Mitochondrial Oxidation ◽  
Adipose Tissue Lipolysis

Fatty acids derived from adipose tissue lipolysis, intramyocellular triacylglycerol lipolysis, or de novo lipogenesis serve a variety of functions in skeletal muscle. The two major fates of fatty acids are mitochondrial oxidation to provide energy for the myocyte and storage within a variety of lipids, where they are stored primarily in discrete lipid droplets or serve as important structural components of membranes. In this review, we provide a brief overview of skeletal muscle fatty acid metabolism and highlight recent notable advances in the field. We then 1) discuss how lipids are stored in and mobilized from various subcellular locations to provide adaptive or maladaptive signals in the myocyte and 2) outline how lipid metabolites or metabolic byproducts derived from the actions of triacylglycerol metabolism or β-oxidation act as positive and negative regulators of insulin action. We have placed an emphasis on recent developments in the lipid biology field with respect to understanding skeletal muscle physiology and discuss unanswered questions and technical limitations for assessing lipid signaling in skeletal muscle.

A comparison of fuel preferences of mitochondria from vertebrates and invertebrates

1990 ◽  
Vol 68 (7) ◽  
pp. 1337-1349 ◽  
Author(s):  
C. D. Moyes ◽  
R. K. Suarez ◽  
P. W. Hochachka ◽  
J. S. Ballantyne
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Fatty Acids ◽  
Energy Metabolism ◽  
Ketone Bodies ◽  
Mitochondrial Enzymes ◽  
Tissue Specific ◽  
Isolated Mitochondria ◽  
Mitochondrial Oxidation ◽  
Aerobic Energy Metabolism

Knowledge of tissue-specific mitochondrial properties is important in understanding cellular aerobic energy metabolism. Studies employing isolated mitochondria offer the advantage of direct and controlled manipulation of extramitochondrial conditions, while minimizing disruption of interactions between mitochondrial enzymes, transporters, and membranes. In this review, we compare the oxidative properties of mitochondria isolated from liver, heart, and skeletal muscle of vertebrates and invertebrates. The observed differences between tissues and species in the capacities for mitochondrial oxidation of fatty acids, ketone bodies, pyruvate, and amino acids reflect fundamentally different adaptations for the assimilation, storage, and utilization of metabolic fuels.

scholarly journals Ketones, omega-3 fatty acids and the Yin-Yang balance in the brain: insights from infant development and Alzheimer’s disease, and implications for human brain evolution

OCL ◽  
2018 ◽  
Vol 25 (4) ◽  
pp. D409 ◽  
Author(s):  
Stephen C. Cunnane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Energy Metabolism ◽  
Brain Evolution ◽  
Human Brain Evolution ◽  
Infant Brain ◽  
Infant Brain Development ◽  
The Brain ◽  
Brain Energy

Optimal brain performance is intimately linked to the brain’s Yin and the Yang − the balance between its structure and its energy metabolism. This relationship is clearly exemplified in infant brain development and in Alzheimer’s disease, and probably also applies to human brain evolution. In these examples, redundant pathways help achieve this important balance. For instance, the key structural lipid for the brain, docosahexaenoic acid (DHA), is supplied to the infant brain from at last three overlapping sources: (i) milk; (ii) infant’s own fat stores and (iii) by some endogenous synthesis from α-linolenic acid (ALA) or eicosapentaenoic acid (EPA). On the energy side, glucose is normally the brain’s main fuel but under conditions of prolonged starvation, it can be almost totally replaced by the ketone bodies, acetoacetate and β-hydroxybutyrate. When ketones are present in the blood they spare glucose uptake by the brain because they are actually the brain’s preferred fuel and are essential for normal infant brain development. The redundant sources of ketones are long chain fatty acids (including the relatively ketogenic ALA) in infant stores, and medium chain triglycerides (MCT) in milk. Besides infancy, nowhere is the strain on the brain’s balance between yin and yang more apparent than in Alzheimer’s disease (AD). One of the reasons why attempts to treat AD have largely failed could well be because chronically inadequate glucose supply to some areas of the brain on the order of 10% is present in people at risk of AD long before cognitive decline begins. However, brain ketone uptake is still normal even in moderately advanced AD. Hence, treatments that ignore the brain energy (glucose) deficit in AD would be predicted to fail, but treatments that attempt to rescue brain fuel availability via ketones would be predicted to have a better chance of succeeding. By analogy to ketones sparing glucose for brain energy metabolism, perhaps ALA or EPA entering the brain can help spare (conserve) DHA for its structural role. If so, it would not necessarily be futile to transport ALA and EPA into the brain just to β-oxidize the majority afterwards; DHA sparing as well as ketone production could be important beneficiaries.

scholarly journals Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations

2020 ◽  
Vol 11 ◽  
pp. 204062232094477
Author(s):  
Bimala Malla ◽  
Samuel Cotten ◽  
Rebecca Ulshoefer ◽  
Friedemann Paul ◽  
Anja E. Hauser ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Conformational Changes ◽  
De Novo ◽  
Mitochondrial Dynamics ◽  
Neuroprotective Effect ◽  
Oxidation Potential ◽  
Mitochondrial Activity ◽  
The Central Nervous System ◽  
Spinal Roots ◽  
Mitochondrial Oxidation

Mitochondrial dysfunction is a common pathological hallmark in various inflammatory and degenerative diseases of the central nervous system, including multiple sclerosis (MS). We previously showed that oxidative stress alters axonal mitochondria, limiting their transport and inducing conformational changes that lead to axonal damage. Teriflunomide (TFN), an oral immunomodulatory drug approved for the treatment of relapsing forms of MS, reversibly inhibits dihydroorotate dehydrogenase (DHODH). DHODH is crucial for de novo pyrimidine biosynthesis and is the only mitochondrial enzyme in this pathway, thus conferring a link between inflammation, mitochondrial activity and axonal integrity. Here, we investigated how DHODH inhibition may affect mitochondrial behavior in the context of oxidative stress. We employed a model of transected murine spinal roots, previously developed in our laboratory. Using confocal live imaging of axonal mitochondria, we showed that in unmanipulated axons, TFN increased significantly the mitochondria length without altering their transport features. In mitochondria challenged with 50 µM hydrogen peroxide (H2O2) to induce oxidative stress, the presence of TFN at 1 µM concentration was able to restore mitochondrial shape, motility, as well as mitochondrial oxidation potential to control levels. No effects were observed at 5 µM TFN, while some shape and motility parameters were restored to control levels at 50 µM TFN. Thus, our data demonstrate an undescribed link between DHODH and mitochondrial dynamics and point to a potential neuroprotective effect of DHODH inhibition in the context of oxidative stress-induced damage of axonal mitochondria.

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