Energy Metabolism in the Brain

Dienel, Gerald A.

doi:10.1016/b978-0-12-397179-1.00003-8

Cited by 26 publications

(66 citation statements)

References 301 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The adult human brain weighs approximately 2% of the total body weight and consumes 25% of the total body glucose consumption and 20% of the oxygen consumption. More precisely, the cerebral metabolic rate of glucose consumption (CMR glc ) and oxygen (CMRO 2 ) in the adult brain is 31 pmol/100 g/min and 156 pmol/100 g/min, respectively . The ratio of CMRO 2 /CMR glc at resting state is approximately 5.5, which is close to 6.0, the theoretical stoichiometry for the complete oxidation of glucose with oxygen (C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O).…”

Section: Glucose and Lacatementioning

confidence: 61%

“…The measured data indicate that almost all glucose is metabolized oxidatively except for the consumption of some additional glucose for non‐oxidative metabolism. In fact, the brain is strictly dependent on glucose for its energy production . High CMRO 2 and CMR glc levels produce ATP efficiently with a ratio of 6.0, driving Na + ,K + ‐ATPase to maintain a steep ionic gradient across the cellular membrane.…”

Section: Glucose and Lacatementioning

confidence: 99%

“…The maintenance of the GSH concentration is dependent on nicotinamide adenine dinucleotide phosphate (NADPH), a product of the pentose‐phosphate pathway (PPP), which is a shunt pathway of glycolysis (Fig. ) . Therefore, the influx to the PPP in glycolysis is an index of PPP activity and reflects the anti‐oxidative function of many kinds of cells.…”

Section: Glucose and Lacatementioning

confidence: 99%

“…Therefore, the influx to the PPP in glycolysis is an index of PPP activity and reflects the anti‐oxidative function of many kinds of cells. PPP flux is regulated by glucose‐6‐phosphate dehydrogenase (G6PDH), which is a rate‐limiting enzyme of this shunt pathway . The basal influx to the PPP in astroglia is approximately seven times as high as that in neurons, suggesting that glycolysis has anti‐oxidative roles in astroglia …”

Section: Glucose and Lacatementioning

confidence: 99%

See 3 more Smart Citations

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

View full text Add to dashboard Cite

Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and microvasculature in the brain gray matter. They play a pivotal role in brain metabolism as well as in the regulation of cerebral blood flow, taking advantage of their unique anatomical location. In particular, the astroglial cellular metabolic compartment exerts supportive roles in dedicating neurons to the generation of action potentials and protects them against oxidative stress associated with their high energy consumption. An impairment of normal astroglial function, therefore, can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuroimmunological diseases, in which metabolic derangements accelerate neuronal damage. The neurovascular unit (NVU), the major components of which include neurons, microvessels, and astroglia, is a conceptual framework that was originally used to better understand the pathophysiology of cerebral ischemia. At present, the NVU is a tool for understanding normal brain physiology as well as the pathophysiology of numerous neurological disorders. The metabolic responses of astroglia in the NVU can be either protective or deleterious. This review focuses on three major metabolic compartments: (i) glucose and lactate; (ii) fatty acid and ketone bodies; and (iii) D‐ and L‐serine. Both the beneficial and the detrimental roles of compartmentalization between neurons and astroglia will be discussed. A better understanding of the astroglial metabolic response in the NVU is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.

show abstract

Section: Glucose and Lacatementioning

confidence: 61%

Section: Glucose and Lacatementioning

confidence: 99%

Section: Glucose and Lacatementioning

confidence: 99%

Section: Glucose and Lacatementioning

confidence: 99%

See 2 more Smart Citations

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

View full text Add to dashboard Cite

show abstract

“…Brain function is exclusively dependent on the oxidative metabolism of glucose (Clarke and Sokoloff, 1999; Dienel, 2009). Even though the theoretical ratio of the CMR oxy (cerebral metabolic rate of oxygen) and the CMR glc (cerebral metabolic rate of glucose) for the complete oxidation of glucose is 6, the values measured in the human brain during a non-activated, steady state are always lower than 6 (5.0–5.5), indicating that more glucose is consumed than oxidized.…”

Section: Introductionmentioning

confidence: 99%

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

2012

View full text Add to dashboard Cite

ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke.

show abstract

Selective vulnerability of hippocampal CA1 and CA3 pyramidal cells: What are possible pathomechanisms and should more attention be paid to the CA3 region in future studies?

Einenkel,

Salameh

2023

J of Neuroscience Research

View full text Add to dashboard Cite

Transient ischemia and reperfusion selectively damage neurons in brain, with hippocampal pyramidal cells being particularly vulnerable. Even within hippocampus, heterogeneous susceptibility is evident, with higher vulnerability of CA1 versus CA3 neurons described for several decades. Therefore, numerous studies have focused exclusively on CA1. Pediatric cardiac surgery is increasingly focusing on studies of hippocampal structures, and a negative impact of cardiopulmonary bypass on the hippocampus cannot be denied. Recent studies show a shift in selective vulnerability from neurons of CA1 to CA3. This review shows that cell damage is increased in CA3, sometimes stronger than in CA1, depending on several factors (method, species, age, observation period). Despite a highly variable pattern, several markers illustrate greater damage to CA3 neurons than previously assumed. Nevertheless, the underlying cellular mechanisms have not been fully deciphered to date. The complexity is reflected in possible pathomechanisms discussed here, with numerous factors (NMDA, kainate and AMPA receptors, intrinsic oxidative stress potential and various radicals, AKT isoforms, differences in vascular architecture, ratio of pro‐ and anti‐apoptotic Bcl‐2 factors, vulnerability of interneurons, mitochondrial dysregulation) contributing to either enhanced CA1 or CA3 vulnerability. Furthermore, differences in expressed genome, proteome, metabolome, and transcriptome in CA1 and CA3 appear to influence differential behavior after damaging stimuli, thus metabolomics‐, transcriptomics‐, and proteomics‐based analyses represent a viable option to identify pathways of selective vulnerability in hippocampal neurons. These results emphasize that future studies should focus on the CA3 field in addition to CA1, especially with regard to improving therapeutic strategies after ischemic/hypoxic brain injury.

show abstract

Energy Metabolism in the Brain

Cited by 26 publications

References 301 publications

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

Selective vulnerability of hippocampal CA1 and CA3 pyramidal cells: What are possible pathomechanisms and should more attention be paid to the CA3 region in future studies?

Contact Info

Product

Resources

About