Long Lasting High Lysine Diet Aggravates White Matter Injury in Glutaryl-CoA Dehydrogenase Deficient (Gcdh-/-) Mice

Molecular Neurobiology
Silvia Olivera-BravoMoacir Wajner

Abstract

Glutaric acidemia type I (GA-I) is a neurometabolic disease caused by deficient activity of glutaryl-CoA dehydrogenase (GCDH) that results in accumulation of metabolites derived from lysine (Lys), hydroxylysine, and tryptophan catabolism. GA-I patients typically develop encephalopatic crises with striatal degeneration and progressive white matter defects. However, late onset patients as well as Gcdh-/- mice only suffer diffuse myelinopathy, suggesting that neuronal death and white matter defects are different pathophysiological events. To test this hypothesis, striatal myelin was studied in Gcdh-/- mice fed from 30 days of age during up to 60 days with a diet containing normal or moderately increased amounts of Lys (2.8%), which ensure sustained elevated levels of GA-I metabolites. Gcdh-/- mice fed with 2.8% Lys diet showed a significant decrease in striatal-myelinated areas and progressive vacuolation of white matter tracts, as compared with animals fed with normal diet. Myelin pathology increased with the time of exposure to high Lys diet and was also detected in 90-day old Gcdh-/- mice fed with normal diet, suggesting that dietary Lys accelerated the undergoing white matter damage. Gcdh-/- mice fed with 2.8% Lys diet also sh...Continue Reading

References

Jun 1, 1975·Biochemical Medicine·S I Goodman, J G Kohlhoff
Feb 1, 1992·Journal of the Neurological Sciences·D SofferS Gottschalk-Sabag
Jul 31, 2003·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Kevin A Strauss, D Holmes Morton
Oct 27, 2004·Journal of Inherited Metabolic Disease·D M KoellerS Kölker
Jan 25, 2005·Nature Cell Biology·Shinichi KondoKazunori Imaizumi
Feb 4, 2005·Brain : a Journal of Neurology·Christopher B R FunkMarc R Del Bigio
Apr 21, 2005·The Journal of Biological Chemistry·Sven W SauerStefan Kölker
Feb 1, 2006·Brain : a Journal of Neurology·William J ZinnantiKeith C Cheng
May 5, 2007·Brain : a Journal of Neurology·Kevin A StraussD Holmes Morton
Oct 13, 2007·The Journal of Clinical Investigation·William J ZinnantiKeith C Cheng
Feb 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Younjin MinJacob Israelachvili
May 13, 2009·Brain : a Journal of Neurology·Inga HartingStefan Kölker
Oct 23, 2009·Acta Neuropathologica·Monika Bradl, Hans Lassmann
Apr 2, 2011·The Journal of Biological Chemistry·Jessica LampChris Mühlhausen
Feb 13, 2013·Journal of Neurochemistry·George Harauz, Joan M Boggs
Dec 4, 2013·Neurotoxicity Research·Silvia Olivera-BravoLuis Barbeito
Jan 7, 2015·Biochimica Et Biophysica Acta·Sven W SauerStefan Kölker
Mar 30, 2016·Brain Research·Oliver J Freeman, Giovanna R Mallucci
Apr 14, 2016·Experimental Neurology·Ian D Duncan, Abigail B Radcliff
Oct 8, 2016·Advances in Experimental Medicine and Biology·Silvia Olivera-BravoLuigi Barbeito

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Citations

May 28, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Moacir WajnerBianca Seminotti
Mar 28, 2019·Nature Reviews. Neurology·Moacir Wajner

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