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4.5 Coupling of Brain Function to Metabolism: Evaluation of Energy Requirements

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

There is no rigid association in vivo between changes of oxygen consumption, glucose combustion, and blood flow in the human brain. The claim that cerebral blood flow rises to satisfy the demands for oxygen and glucose during neuronal excitation therefore is simplistic.  Energy budget estimates indicate that most of the cerebral energy demand reflects the steady-state level of graded post-synaptic membrane depolarization, followed by action potential generation and propagation. Increased energy supply is required to maintain the depolarization of neuronal membranes when sodium and potassium conductances are increased. Glucose, pyruvate and lactate occupy single tissue compartments, but transient shifts of the relative activity of neurons and astrocytes disrupt the steady-state, and the properties of lactate dehydrogenase mayy vary temporally, as dictated by transient shifts of cytosolic redox potentials and pH values. Pyruvate and lactate generation invariably occurs when astrocytes are activated by glutamate release. In these cases, the increased demand for glutamate imposes a metabolic rate on astroglial cells that exceeds their modest oxidative capacity. Although the resulting pyruvate and lactate accumulation is influenced by lactate export or import across the blood-brain barrier, pyruvate and lactate accumulate in a joint pool, to which astrocytes produce more pyruvate than neurons. The blood flow increase appears to be coupled to the rate of glycolysis. There is increasing evidence that the putative mechanism underlying the flow-glycolysis couple resides in astrocytes. The evidence suggests that the increase of oxidative metabolism in neurons is coupled to a rise of pyruvate, as dictated by the degree of mitochondrial activation. Under some circumstances, regional ‘peaks’ of increased blood flow and increased oxygen consumption could be dissociated by the differential activation of primary and secondary neuronal networks. The activations accompanying the most complex processing of information could be those with the tightest coupling between oxygen consumption and blood flow and hence with the least generation of lactate.

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Abbreviations

AA:

arachidonic acid

ADP:

adenosine diphosphate

AMP:

adenosine monophosphate

A/N:

astrocyte-to-neuron activation ratio, relative to baseline

ATP:

adenosine triphosphate

avd:

arteriovenous deficit

CBF:

cerebral blood flow

CK:

creatine kinase

CMRglc :

cerebral metabolic rate of glucose

CMRO2 :

cerebral metabolic rate of oxygen

CO2 art :

arterial oxygen concentration

COX:

cyclooxygenase

CYP4A:

cytochrome P450 4A, enzymes

EAAT:

excitatory amino acid transporter

EET:

epoxyeicosatrienoate

E O2 :

oxygen extraction fraction

FADH2 :

flavin adenine dinucleotide

f glc :

fraction of ATP, generated non-oxidatively

f O2 :

fraction of ATP, generated oxidatively

GLAST:

glutamate astrocyte-specific transporter

glc:

glucose

GLT:

glutamate transporter

GLUT:

glucose transporter

GTP:

guanosine triphosphate

20-HETE:

20-hydroxyeicosatetraenoate

hg:

hectogram

H4 LDH:

heart type

HK:

hexokinase

J glc :

glucose metabolic rate

J max :

maximum metabolite flux

J O2 :

oxygen metabolic rate

K M :

K m Michaelis half-saturation constant

L :

oxygen conductivity of tissue

lact:

lactate

LD:

lactate dehydrogenase subtype

LDH:

lactate dehydrogenase

LGI:

lactate-glucose index

M4:

LDH, muscle type

MAI:

metabolite accumulation index

MCT:

monocarboxylic acid transporter

MGI:

metabolites-glucose index

mGluR:

metabotropic glutamate receptor

Mi-CK:

mitochondrial creatine kinase

mMCT:

mitochondrial monocarboxylic acid transporter

mmHg:

millimeter Mercury

mRNA:

messenger RNA, (ribonucleic acid)

MUR:

metabolite uptake ratio

NAD+ :

nicotinamide adenine dinucleotide (oxidized form)

NADH:

nicotinamide adenine dinucleotide (reduced form)

NSI:

non-steady-state index

NO:

nitric oxide

NOS:

nitric oxide synthase

OGI:

oxygen-glucose index

P 50 :

half-saturation oxygen tension

P 50 cytox :

half-saturation oxygen tension of cytochrome oxidase

PCr:

phosphocreatine

PDH:

pyruvate dehydrogenase

PFK:

phosphofructokinase

PGE2:

prostaglandin E2

Pi :

inorganic phosphate

P O2 :

oxygen partial pressure (tension)

p R :

reaction potential

pyr:

pyruvate

S :

saturation

TCA:

tricarboxylic acid

T max :

maximum transporter-mediated flux

V max :

maximum enzyme reaction velocity

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Acknowledgments

The author wishes to thank the Medical Research Councils of Canada and Denmark and the National Science Foundation of Denmark for support.

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  1. A. Gjedde
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  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA

    Gary E. Gibson Ph.D. (Professor of Neuroscience Department of Neurology and Neuroscience) (Professor of Neuroscience Department of Neurology and Neuroscience)

  3. Dept. Neurology and Physiology & Biophysics, University Arkansas for Medical Sciences, Shorey Bldg. Room 715, Mail Slot 830 4301 W. Markham St., Little Rock, AR, 72205, USA

    Gerald A. Dienel Ph.D. (Professor) (Professor)

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Gjedde, A. (2007). 4.5 Coupling of Brain Function to Metabolism: Evaluation of Energy Requirements. In: Lajtha, A., Gibson, G.E., Dienel, G.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30411-3_14

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