Energy Metabolism Impairment in Migraine

2019 ◽  
Vol 26 (34) ◽  
pp. 6253-6260 ◽  
Author(s):  
Sabina Cevoli ◽  
Valentina Favoni ◽  
Pietro Cortelli
Keyword(s):  
Energy Metabolism ◽  
Energy Demand ◽  
Energy Production ◽  
Mitochondrial Respiratory Chain ◽  
Migraine Prophylaxis ◽  
Resonance Spectroscopy ◽  
Oxidative Energy Metabolism ◽  
Spectroscopy Studies ◽  
The Brain ◽  
Brain Energy

Migraine is a common disabling neurological disorder which is characterised by a recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an updated overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine.

Magnetic Resonance Spectroscopy in Migraine

Cephalalgia ◽  
1995 ◽  
Vol 15 (4) ◽  
pp. 323-327 ◽  
Author(s):  
P Montagna
Keyword(s):  
Energy Metabolism ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Energy Demand ◽  
Low Energy ◽  
Resonance Spectroscopy ◽  
Non Invasive ◽  
Relevant Role ◽  
Brain Ph ◽  
Brain Energy

31-phosphorus Magnetic Resonance Spectroscopy (MRS) is a technique developed for the non-invasive study of energy metabolism in living subjects. It determines the concentrations of high and low energy phosphates in resting and activated conditions, and of intracellular pH. 31P-MRS has been applied to the study of migraine, both during and in between attacks. Intracellular brain pH remains unchanged during the migraine attack, suggesting that ischemia does not play a relevant role in the origin of the neuro-logical signs. During and in-between attacks, migraineurs display abnormalities in energy metabolism of brain and muscle, consisting of reduced levels of phosphocreatine, reduced cellular-free energy and increased rate of ATP biosynthesis. We suggest that these abnormalities in energy metabolism predispose migraineurs to develop an attack under conditions of increased brain energy demand.

Magnetic Resonance Spectroscopy Studies in Migraine

Cephalalgia ◽  
1994 ◽  
Vol 14 (3) ◽  
pp. 184-193 ◽  
Author(s):  
P Montagna ◽  
P Cortelli ◽  
B Barbiroli
Keyword(s):  
Energy Metabolism ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Muscle Energy ◽  
Spectroscopy Studies ◽  
Muscle Energy Metabolism ◽  
Impaired Energy Metabolism ◽  
Brain Energy

We describe the method of 31phosphorous magnetic resonance spectroscopy and review the results when it is applied to the study of brain and muscle energy metabolism in migraine subjects. Brain energy metabolism appears to be abnormal in all major subtypes of migraine when measured both during and between attacks. Impaired energy metabolism is also documented in skeletal muscle. We suggest that migraine is associated with a generalized disorder of mitochondrial oxidative phosphorylation and that this may constitute a threshold for the triggering of migraine attacks.

scholarly journals Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

2017 ◽  
Vol 38 (10) ◽  
pp. 1754-1768 ◽  
Author(s):  
Michaela C Hohnholt ◽  
Vibe H Andersen ◽  
Jens V Andersen ◽  
Sofie K Christensen ◽  
Melis Karaca ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Glutamate Dehydrogenase ◽  
Energy Demand ◽  
Glucose Deprivation ◽  
Brain Mitochondria ◽  
Glutamine Metabolism ◽  
Oxidative Deamination ◽  
Oxidative Energy Metabolism ◽  
The Brain

The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of glutamate to α-ketoglutarate accompanied by a reduction of NAD+ to NADH. GDH connects amino acid, carbohydrate, neurotransmitter and oxidative energy metabolism. Glutamine is a neurotransmitter precursor used by neurons to sustain the pool of glutamate, but glutamine is also vividly oxidized for support of energy metabolism. This study investigates the role of GDH in neuronal metabolism by employing the Cns- Glud1−/− mouse, lacking GDH in the brain (GDH KO) and metabolic mapping using 13C-labelled glutamine and glucose. We observed a severely reduced oxidative glutamine metabolism during glucose deprivation in synaptosomes and cultured neurons not expressing GDH. In contrast, in the presence of glucose, glutamine metabolism was not affected by the lack of GDH expression. Respiration fuelled by glutamate was significantly lower in brain mitochondria from GDH KO mice and synaptosomes were not able to increase their respiration upon an elevated energy demand. The role of GDH for metabolism of glutamine and the respiratory capacity underscore the importance of GDH for neurons particularly during an elevated energy demand, and it may reflect the large allosteric activation of GDH by ADP.

scholarly journals The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia

2012 ◽  
Vol 34 (3) ◽  
pp. 121-128 ◽  
Author(s):  
Rodrigo Barbachan Mansur ◽  
Elisa Brietzke
Keyword(s):  
Bipolar Disorder ◽  
Energy Metabolism ◽  
Energy Supply ◽  
Clinical Implications ◽  
Metabolic Abnormalities ◽  
Compensatory Mechanisms ◽  
High Prevalence ◽  
Brain Theory ◽  
The Brain ◽  
Brain Energy

Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses.

scholarly journals Aspartoacylase Supports Oxidative Energy Metabolism during Myelination

2012 ◽  
Vol 32 (9) ◽  
pp. 1725-1736 ◽  
Author(s):  
Jeremy S Francis ◽  
Louise Strande ◽  
Vladamir Markov ◽  
Paola Leone
Keyword(s):  
Energy Metabolism ◽  
Postnatal Development ◽  
Strong Association ◽  
Canavan Disease ◽  
Lipid Synthesis ◽  
Systematic Analysis ◽  
Early Postnatal Development ◽  
Neuronal Viability ◽  
Oxidative Energy Metabolism ◽  
The Brain

The inherited leukodystrophy Canavan disease arises due to a loss of the ability to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major point of focus for efforts to define NAA function. Accumulation of noncatabolized NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA associated with compromised neuronal integrity in a broad spectrum of other clinical conditions. Experimental evidence for NAA function supports a role in white matter lipid synthesis, but does not explain how both elevated and lowered NAA can be associated with pathology in the brain. We have undertaken a systematic analysis of postnatal development in a mouse model of Canavan disease that delineates development and pathology by identifying markers of oxidative stress preceding oligodendrocyte loss and dysmyelination. These data suggest a role for NAA in the maintenance of metabolic integrity in oligodendrocytes that may be of relevance to the strong association between NAA and neuronal viability. N-acetylaspartic acid is proposed here to support lipid synthesis and energy metabolism via the provision of substrate for both cellular processes during early postnatal development.

Abstract 276: Angiotensin AT1 Receptor Blockade Reverses Age-Related Changes in Myocardial Energy Metabolism and Increases Mitochondrial Biogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Peter M Abadir ◽  
Ashwin Akki ◽  
Robert Carey ◽  
Ashish Gupta ◽  
Vadappuram Chacko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Mitochondrial Biogenesis ◽  
Energy Production ◽  
Nuclear Gene ◽  
At1 Receptor ◽  
Resonance Spectroscopy ◽  
Receptor Blockade ◽  
Lv Mass ◽  
Old Mice

Aging and mitochondrial function have been closely linked. We recently reported the identification of a mitochondrial angiotensin system. We hypothesized that angiotensin AT1 receptor blockade would increase energy production and mitochondrial biogenesis and reduce oxidative stress in aging hearts. We used Magnetic resonance spectroscopy to measure cardiac energy metabolism and function in young (20 wks old), aged (150 wks old) mice at baseline and after 4 weeks of losartan (50 mg/kg/day). For mitobiogenesis, qPCR was used to calculate CytB (mitochondrial gene)/GAPDH (nuclear gene) ratio and to measure mito-survival genes Sirt1, Sirt3, Nampt, and PGC-1α. Cardiomyocyte mitochondria from young, aged and treated mice were examined with electron microscopy. The expression of nitrotyrosine was quantified by immunohistochemistry. Older animals hearts (n=9) exhibited increase in LV mass (103±9 mg versus 120±8 mg, young (n=8) versus old (n=9), P<0.002). The mean cardiac PCr/ATP was reduced in older animals (1.5±0.2) than that of young mice (2.0±0.3, P<0.0004). Losartan abolished the LV mass increase in older animals (109±11 mg vs 101±7 mg, young versus old, P<0.1) and improved the impaired energy metabolism of the older hearts increasing the PCr/ATP ratios towards those observed in younger animals (1.94±0.01 vs 1.87±0.4, control versus old, P<0.7). Losartan increased EF in older animals (56±5% vs 63±5%, old versus old treated, P<0.01). Losartan increased mitobiogenesis in the hearts of treated young and old mice (3.8+2.5 folds, P<0.02 and 4.3+ 0.9 folds, P<0.0001). Mito-survival genes in the heart were not increased but PGC-1α was up-regulated by 2.8+1.6-fold, P<0.05 and 7+ 1.9-fold, P<0.001 in young and old treated mice. Electron micrograph analysis revealed that aging was associated with swollen cardiac mitochondria and disrupted cristae, which were reversed by Losartan. Losartan in older animals significantly reduced oxidative damage as evidenced by less Nitrotyrosine staining score in cardiomyocytes (2.5±0.5 vs. 1.3±0.4, old versus old treated, P<0.0009). Our results indicate that Losartan in aging increased mitobiogenesis, reduced oxidative stress, improved energy production and restored cardiac function to the healthy young adult level.

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