Energy Metabolism in the Brain

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.

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Aspartoacylase Supports Oxidative Energy Metabolism during Myelination

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.66 ◽

2012 ◽

Vol 32 (9) ◽

pp. 1725-1736 ◽

Cited By ~ 24

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.

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Biochemical Effects of Cerebral Ischemia: Relevance To Migraine

Cephalalgia ◽

10.1177/03331024850050s206 ◽

1985 ◽

Vol 5 (2_suppl) ◽

pp. 35-42 ◽

Cited By ~ 4

Author(s):

KMA Welch ◽

JA Helpern ◽

JR Ewing ◽

WM Robertson ◽

G D'Andrea

Keyword(s):

Energy Metabolism ◽

Cerebral Ischemia ◽

Spreading Depression ◽

Metabolic Depression ◽

Ischemia And Reperfusion ◽

Phosphate Metabolism ◽

Biochemical Effects ◽

The Brain ◽

Intracranial Circulation

Although decreased CBF has now been reported during the prodrome of migraine, the cause of the decreased flow is still unknown. It is particularly unclear whether these phenomena are related to vasospasm and “steal” between the extracranial and intracranial circulation or to the spreading depression of Leao and the accompanying metabolic depression. In the present paper, metabolic changes in the brain during ischemia and reperfusion are reviewed and compared with CNS biochemical changes during migraine attack. In addition, the technique of Topical Magnetic Resonance (TMR) as applied to the in vivo study of energy phosphate metabolism in extracranial tissues and brain is described and the potential of this technique to evaluate shifts in energy metabolism and pH in stroke and migraine is discussed.

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Prolonged anoxic survival due to anoxia pre-exposure: brain ATP, lactate, and pyruvate

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.207.2.452 ◽

1964 ◽

Vol 207 (2) ◽

pp. 452-456 ◽

Cited By ~ 76

Author(s):

Nancy Ann Dahl ◽

William M. Balfour

Keyword(s):

Energy Metabolism ◽

Survival Time ◽

Glucose Concentration ◽

Prolonged Survival ◽

Anaerobic Glycolysis ◽

Cerebral Energy Metabolism ◽

Atp Concentration ◽

Lactate And Pyruvate ◽

The Brain

Rats subjected to a brief anoxia can survive go sec in a second anoxia, compared to a 60-sec survival time of control animals. Slower disappearance of ATP concentration in the brain during the second exposure indicates this longer survival is due to an altered cerebral energy metabolism. Initial cerebral ATP concentration is no higher in pre-exposed animals than in controls. When glycolysis is inhibited by iodoacetate before testing in anoxia, the advantage of pre-exposure disappears, suggesting the longer survival may be due to increased anacrobic glycolysis. Lactate accumulates faster during anoxia in the brains of pre-exposed animals than in controls, suggesting that increased anaerobic glycolysis is the cause of the prolonged survival. This effect is not due to increased cerebral glucose concentration. A possible reason for this increased glycolysis, and thus the prolonged survival, could be an increase of a compound, such as pyruvate, capable of oxidizing NADH. The initial pyruvate is higher in pre-exposed animals than in controls and injection of pyruvate increases the survival time slightly.

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Cerebral blood flow and energy metabolism during stress

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.259.2.h269 ◽

1990 ◽

Vol 259 (2) ◽

pp. H269-H280 ◽

Cited By ~ 10

Author(s):

R. M. Bryan

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Energy Metabolism ◽

Adrenergic Receptor ◽

Conditioned Fear ◽

Brain Regions ◽

Stressful Events ◽

Ethanol Withdrawal ◽

Adrenergic Mechanism ◽

The Brain

Many, but not all, stressful events are accompanied by increases in cerebral blood flow and/or energy metabolism. The stressful events include pharmacological paralysis, footshock, conditioned fear, hypotension, hypoglycemia, hypoxia, noise, and ethanol withdrawal. These increases are significant because 1) all brain regions are often affected, i.e., certain stressful events have global effects on cerebral blood flow and energy metabolism; and 2) various stressful events appear to have a common adrenergic mechanism for increasing cerebral blood flow and energy metabolism. The adrenergic mechanism involves beta-adrenergic receptor stimulation by either epinephrine secreted from the adrenal medulla or possibly norepinephrine endogenous to the brain. While adrenergic mechanisms are not the only mechanism controlling flow and metabolism for a given stressful condition, they do appear to be common to many situations. At least part of the increase in cerebral blood flow and energy metabolism during many conditions appears to be the result of the stress response and not directly a result of the condition itself.

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Ion and Energy Metabolism of the Brain at the Cellular Level

International Review of Neurobiology ◽

10.1016/s0074-7742(08)60035-5 ◽

1975 ◽

pp. 141-211 ◽

Cited By ~ 96

Author(s):

Leif Hertz ◽

Arne Schousboe

Keyword(s):

Energy Metabolism ◽

Cellular Level ◽

The Brain

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Energy Metabolism and Histology in the Brain during Combined Hypoxemia and Ischemia

European Neurology ◽

10.1159/000114517 ◽

1971 ◽

Vol 6 (1-6) ◽

pp. 329-334 ◽

Cited By ~ 4

Author(s):

L.G. Salford ◽

J.B. Brierley ◽

F. Plum ◽

B.K. Siesjö

Keyword(s):

Energy Metabolism ◽

The Brain

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Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.4.1772 ◽

1996 ◽

Vol 81 (4) ◽

pp. 1772-1777 ◽

Cited By ~ 27

Author(s):

J. C. Lamanna ◽

M. A. Haxhiu ◽

K. L. Kutina-Nelson ◽

S. Pundik ◽

B. Erokwu ◽

...

Keyword(s):

Energy Metabolism ◽

Brain Stem ◽

Respiratory Depression ◽

Intracellular Ph ◽

Metabolic Changes ◽

Nucleus Ambiguus ◽

Electromyographic Activity ◽

Respiratory Drive ◽

Energy Deficiency ◽

The Brain

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772–1777, 1996.—Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized rats resulted in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within 11 min (range 5–27 min), presumably via central depressant mechanisms. At that time, the brain stems were frozen in situ for metabolic analyses. By using 20-μm lyophilized sections from frozen-fixed brain stem, microregional analyses of ATP, phosphocreatine, lactate, and intracellular pH were made from 1) the ventral portion of the nucleus gigantocellularis and the parapyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) the spinal trigeminal nucleus. At the time of respiratory depression, lactate was elevated threefold in all regions. Both ATP and phosphocreatine were decreased to 50 and 25% of control, respectively. Intracellular pH was more acidic by 0.2–0.4 unit in these regions but was relatively preserved in the chemosensitive regions near the ventral and dorsal medullary surfaces. These results show that hypoxia-induced respiratory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it appears that there was significant energy deficiency in the brain stem after hypoxia-induced respiratory depression had occurred.

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