Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone. / Sorensen, Michael; Walls, Anne Byriel; Dam, Gitte; Bak, Lasse Kristoffer; Andersen, Jens Velde; Ott, Peter; Vilstrup, Hendrik; Schousboe, Arne.

In: Analytical Biochemistry, Vol. 654, 114766, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sorensen, M, Walls, AB, Dam, G, Bak, LK, Andersen, JV, Ott, P, Vilstrup, H & Schousboe, A 2022, 'Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone', Analytical Biochemistry, vol. 654, 114766. https://doi.org/10.1016/j.ab.2022.114766

APA

Sorensen, M., Walls, A. B., Dam, G., Bak, L. K., Andersen, J. V., Ott, P., Vilstrup, H., & Schousboe, A. (2022). Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone. Analytical Biochemistry, 654, [114766]. https://doi.org/10.1016/j.ab.2022.114766

Vancouver

Sorensen M, Walls AB, Dam G, Bak LK, Andersen JV, Ott P et al. Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone. Analytical Biochemistry. 2022;654. 114766. https://doi.org/10.1016/j.ab.2022.114766

Author

Sorensen, Michael ; Walls, Anne Byriel ; Dam, Gitte ; Bak, Lasse Kristoffer ; Andersen, Jens Velde ; Ott, Peter ; Vilstrup, Hendrik ; Schousboe, Arne. / Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone. In: Analytical Biochemistry. 2022 ; Vol. 654.

Bibtex

@article{512ad42f48404577adb599013285a4c0,
title = "Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone",
abstract = "Hepatic encephalopathy (HE) is a frequent and devastating but generally reversible neuropsychiatric compli-cation secondary to chronic and acute liver failure. During HE, brain energy metabolism is markedly reduced and it remains unclear whether this is due to external or internal energy supply limitations, or secondary to depressed neuronal cellular functions -and if so, which mechanisms that are in play. The extent of deteriorated cerebral function correlates to blood ammonia levels but the metabolic link to ammonia is not clear. Early studies sug-gested that high levels of ammonia inhibited key tricarboxylic acid (TCA) cycle enzymes thus limiting mito-chondrial energy production and oxygen consumption; however, later studies by us and others showed that this is not the case in vivo. Here, based on a series of translational studies from our group, we advocate the view that the low cerebral energy metabolism of HE is likely to be caused by neuronal metabolic depression due to an elevated GABAergic tone rather than by restricted energy availability. The increased GABAergic tone seems to be secondary to synthesis of large amounts of glutamine in astrocytes for detoxification of ammonia with the glutamine acting as a precursor for elevated neuronal synthesis of vesicular GABA.",
keywords = "Cerebral energy metabolism, Hyperammonemia, Functional imaging, Cell cultures, Isotopes, ACUTE LIVER-FAILURE, GLUTAMINE-SYNTHETASE, OXYGEN-METABOLISM, BLOOD-FLOW, BRAIN, CIRRHOSIS, RATS, HYPERAMMONEMIA, N-13-AMMONIA, DETOXIFICATION",
author = "Michael Sorensen and Walls, {Anne Byriel} and Gitte Dam and Bak, {Lasse Kristoffer} and Andersen, {Jens Velde} and Peter Ott and Hendrik Vilstrup and Arne Schousboe",
year = "2022",
doi = "10.1016/j.ab.2022.114766",
language = "English",
volume = "654",
journal = "Analytical Biochemistry",
issn = "0003-2697",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Low cerebral energy metabolism in hepatic encephalopathy reflects low neuronal energy demand. Role of ammonia-induced increased GABAergic tone

AU - Sorensen, Michael

AU - Walls, Anne Byriel

AU - Dam, Gitte

AU - Bak, Lasse Kristoffer

AU - Andersen, Jens Velde

AU - Ott, Peter

AU - Vilstrup, Hendrik

AU - Schousboe, Arne

PY - 2022

Y1 - 2022

N2 - Hepatic encephalopathy (HE) is a frequent and devastating but generally reversible neuropsychiatric compli-cation secondary to chronic and acute liver failure. During HE, brain energy metabolism is markedly reduced and it remains unclear whether this is due to external or internal energy supply limitations, or secondary to depressed neuronal cellular functions -and if so, which mechanisms that are in play. The extent of deteriorated cerebral function correlates to blood ammonia levels but the metabolic link to ammonia is not clear. Early studies sug-gested that high levels of ammonia inhibited key tricarboxylic acid (TCA) cycle enzymes thus limiting mito-chondrial energy production and oxygen consumption; however, later studies by us and others showed that this is not the case in vivo. Here, based on a series of translational studies from our group, we advocate the view that the low cerebral energy metabolism of HE is likely to be caused by neuronal metabolic depression due to an elevated GABAergic tone rather than by restricted energy availability. The increased GABAergic tone seems to be secondary to synthesis of large amounts of glutamine in astrocytes for detoxification of ammonia with the glutamine acting as a precursor for elevated neuronal synthesis of vesicular GABA.

AB - Hepatic encephalopathy (HE) is a frequent and devastating but generally reversible neuropsychiatric compli-cation secondary to chronic and acute liver failure. During HE, brain energy metabolism is markedly reduced and it remains unclear whether this is due to external or internal energy supply limitations, or secondary to depressed neuronal cellular functions -and if so, which mechanisms that are in play. The extent of deteriorated cerebral function correlates to blood ammonia levels but the metabolic link to ammonia is not clear. Early studies sug-gested that high levels of ammonia inhibited key tricarboxylic acid (TCA) cycle enzymes thus limiting mito-chondrial energy production and oxygen consumption; however, later studies by us and others showed that this is not the case in vivo. Here, based on a series of translational studies from our group, we advocate the view that the low cerebral energy metabolism of HE is likely to be caused by neuronal metabolic depression due to an elevated GABAergic tone rather than by restricted energy availability. The increased GABAergic tone seems to be secondary to synthesis of large amounts of glutamine in astrocytes for detoxification of ammonia with the glutamine acting as a precursor for elevated neuronal synthesis of vesicular GABA.

KW - Cerebral energy metabolism

KW - Hyperammonemia

KW - Functional imaging

KW - Cell cultures

KW - Isotopes

KW - ACUTE LIVER-FAILURE

KW - GLUTAMINE-SYNTHETASE

KW - OXYGEN-METABOLISM

KW - BLOOD-FLOW

KW - BRAIN

KW - CIRRHOSIS

KW - RATS

KW - HYPERAMMONEMIA

KW - N-13-AMMONIA

KW - DETOXIFICATION

U2 - 10.1016/j.ab.2022.114766

DO - 10.1016/j.ab.2022.114766

M3 - Journal article

C2 - 35654134

VL - 654

JO - Analytical Biochemistry

JF - Analytical Biochemistry

SN - 0003-2697

M1 - 114766

ER -

ID: 322785392