Research ExplorerPublicationsIntracerebral accumulation of glutaric and 3-hydroxyglutaric...

Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency

Standard

Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. / Sauer, Sven W; Okun, Jürgen G; Fricker, Gert; Mahringer, Anne; Müller, Ines; Crnic, Linda R; Mühlhausen, Chris; Hoffmann, Georg F; Hörster, Friederike; Goodman, Stephen I; Harding, Cary O; Koeller, David M; Kölker, Stefan.

In: J NEUROCHEM, Vol. 97, No. 3, 05.2006, p. 899-910.

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

Harvard

Sauer, SW, Okun, JG, Fricker, G, Mahringer, A, Müller, I, Crnic, LR, Mühlhausen, C, Hoffmann, GF, Hörster, F, Goodman, SI, Harding, CO, Koeller, DM & Kölker, S 2006, 'Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency', J NEUROCHEM, vol. 97, no. 3, pp. 899-910. https://doi.org/10.1111/j.1471-4159.2006.03813.x

APA

Sauer, S. W., Okun, J. G., Fricker, G., Mahringer, A., Müller, I., Crnic, L. R., Mühlhausen, C., Hoffmann, G. F., Hörster, F., Goodman, S. I., Harding, C. O., Koeller, D. M., & Kölker, S. (2006). Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J NEUROCHEM, 97(3), 899-910. https://doi.org/10.1111/j.1471-4159.2006.03813.x

Vancouver

Sauer SW, Okun JG, Fricker G, Mahringer A, Müller I, Crnic LR et al. Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J NEUROCHEM. 2006 May;97(3):899-910. https://doi.org/10.1111/j.1471-4159.2006.03813.x

Bibtex

@article{6d3c651711004a399b27f5cdbaf15698,
title = "Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency",
abstract = "Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins. As cerebral concentrations of GA and 3-OH-GA have not yet been studied systematically, we investigated the tissue-specific distribution of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart muscle of Gcdh-deficient mice as well as in hepatic Gcdh-/- mice and in C57Bl/6 mice following intraperitoneal loading. Furthermore, we determined the flux of GA and 3-OH-GA across the blood-brain barrier (BBB) using porcine brain microvessel endothelial cells. Concentrations of GA, 3-OH-GA and glutarylcarnitine were significantly elevated in all tissues of Gcdh-/- mice. Strikingly, cerebral concentrations of GA and 3-OH-GA were unexpectedly high, reaching similar concentrations as those found in liver. In contrast, cerebral concentrations of these organic acids remained low in hepatic Gcdh-/- mice and after intraperitoneal injection of GA and 3-OH-GA. These results suggest limited flux of GA and 3-OH-GA across the BBB, which was supported in cultured porcine brain capillary endothelial cells. In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency.",
keywords = "Amino Acids, Animals, Biological Transport, Blood-Brain Barrier, Blotting, Western, Brain, Carnitine, Cells, Cultured, Dicarboxylic Acids, Disease Models, Animal, Endothelial Cells, Glucose, Glutarates, Glutaryl-CoA Dehydrogenase, Heart, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Muscles, Neurodegenerative Diseases, Risk Factors, Statistics, Nonparametric, Swine, Time Factors, Tissue Distribution",
author = "Sauer, {Sven W} and Okun, {J{\"u}rgen G} and Gert Fricker and Anne Mahringer and Ines M{\"u}ller and Crnic, {Linda R} and Chris M{\"u}hlhausen and Hoffmann, {Georg F} and Friederike H{\"o}rster and Goodman, {Stephen I} and Harding, {Cary O} and Koeller, {David M} and Stefan K{\"o}lker",
year = "2006",
month = may,
doi = "10.1111/j.1471-4159.2006.03813.x",
language = "English",
volume = "97",
pages = "899--910",
journal = "J NEUROCHEM",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency

AU - Sauer, Sven W

AU - Okun, Jürgen G

AU - Fricker, Gert

AU - Mahringer, Anne

AU - Müller, Ines

AU - Crnic, Linda R

AU - Mühlhausen, Chris

AU - Hoffmann, Georg F

AU - Hörster, Friederike

AU - Goodman, Stephen I

AU - Harding, Cary O

AU - Koeller, David M

AU - Kölker, Stefan

PY - 2006/5

Y1 - 2006/5

N2 - Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins. As cerebral concentrations of GA and 3-OH-GA have not yet been studied systematically, we investigated the tissue-specific distribution of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart muscle of Gcdh-deficient mice as well as in hepatic Gcdh-/- mice and in C57Bl/6 mice following intraperitoneal loading. Furthermore, we determined the flux of GA and 3-OH-GA across the blood-brain barrier (BBB) using porcine brain microvessel endothelial cells. Concentrations of GA, 3-OH-GA and glutarylcarnitine were significantly elevated in all tissues of Gcdh-/- mice. Strikingly, cerebral concentrations of GA and 3-OH-GA were unexpectedly high, reaching similar concentrations as those found in liver. In contrast, cerebral concentrations of these organic acids remained low in hepatic Gcdh-/- mice and after intraperitoneal injection of GA and 3-OH-GA. These results suggest limited flux of GA and 3-OH-GA across the BBB, which was supported in cultured porcine brain capillary endothelial cells. In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency.

AB - Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins. As cerebral concentrations of GA and 3-OH-GA have not yet been studied systematically, we investigated the tissue-specific distribution of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart muscle of Gcdh-deficient mice as well as in hepatic Gcdh-/- mice and in C57Bl/6 mice following intraperitoneal loading. Furthermore, we determined the flux of GA and 3-OH-GA across the blood-brain barrier (BBB) using porcine brain microvessel endothelial cells. Concentrations of GA, 3-OH-GA and glutarylcarnitine were significantly elevated in all tissues of Gcdh-/- mice. Strikingly, cerebral concentrations of GA and 3-OH-GA were unexpectedly high, reaching similar concentrations as those found in liver. In contrast, cerebral concentrations of these organic acids remained low in hepatic Gcdh-/- mice and after intraperitoneal injection of GA and 3-OH-GA. These results suggest limited flux of GA and 3-OH-GA across the BBB, which was supported in cultured porcine brain capillary endothelial cells. In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency.

KW - Amino Acids

KW - Animals

KW - Biological Transport

KW - Blood-Brain Barrier

KW - Blotting, Western

KW - Brain

KW - Carnitine

KW - Cells, Cultured

KW - Dicarboxylic Acids

KW - Disease Models, Animal

KW - Endothelial Cells

KW - Glucose

KW - Glutarates

KW - Glutaryl-CoA Dehydrogenase

KW - Heart

KW - Liver

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Models, Biological

KW - Muscles

KW - Neurodegenerative Diseases

KW - Risk Factors

KW - Statistics, Nonparametric

KW - Swine

KW - Time Factors

KW - Tissue Distribution

U2 - 10.1111/j.1471-4159.2006.03813.x

DO - 10.1111/j.1471-4159.2006.03813.x

M3 - SCORING: Journal article

C2 - 16573641

VL - 97

SP - 899

EP - 910

JO - J NEUROCHEM

JF - J NEUROCHEM

SN - 0022-3042

IS - 3

ER -