Cellular and molecular outcomes of glutamine supplementation in the brain of succinic semialdehyde dehydrogenase-deficient mice

JIMD Reports
Madalyn N BrownJean-Baptiste Roullet

Abstract

Succinic semialdehyde dehydrogenase deficiency (SSADHD) manifests with low levels of glutamine in the brain, suggesting that central glutamine deficiency contributes to pathogenesis. Recently, we attempted to rescue the disease phenotype of aldh5a1 -/- mice, a murine model of SSADHD with dietary glutamine supplementation. No clinical rescue and no central glutamine improvement were observed. Here, we report the results of follow-up studies of the cellular and molecular basis of the resistance of the brain to glutamine supplementation. We first determined if the expression of genes involved in glutamine metabolism was impacted by glutamine feeding. We then searched for changes of brain histology in response to glutamine supplementation, with a focus on astrocytes, known regulators of glutamine synthesis in the brain. Glutamine supplementation significantly modified the expression of glutaminase (gls) (0.6-fold down), glutamine synthetase (glul) (1.5-fold up), and glutamine transporters (solute carrier family 7, member 5 [slc7a5], 2.5-fold up; slc38a2, 0.6-fold down). The number of GLUL-labeled cells was greater in the glutamine-supplemented group than in controls (P < .05). Reactive astrogliosis, a hallmark of brain inflammatio...Continue Reading

References

Jan 1, 1993·Journal of Inherited Metabolic Disease·G UzielM Savoiardo
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·R J BoadoW M Pardridge
Apr 25, 2000·Neuropediatrics·C YalçinkayaI Küçükercan
May 28, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ulrika WilhelmssonMilos Pekny
Apr 23, 2005·Glia·Milos Pekny, Michael Nilsson
May 27, 2005·Seminars in Cancer Biology·Bryan C Fuchs, Barrie P Bode
Jun 22, 2006·Journal of Neurochemistry·Lasse K BakHelle S Waagepetersen
May 25, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lynsey MeikleDavid J Kwiatkowski
May 15, 2009·Brain : a Journal of Neurology·Olivier QuerbesUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Nov 1, 1978·Neuroscience Letters·J C ReubiM Cuénod
Dec 17, 2009·Acta Neuropathologica·Michael V Sofroniew, Harry V Vinters
Apr 27, 2010·Nature Neuroscience·Pavel I OrtinskiDouglas A Coulter
May 10, 2013·Future Neurology·Alexei VerkhratskyVladimir Parpura
Feb 27, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stefanie RobelHarald Sontheimer
Apr 7, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rita CitraroGiovambattista De Sarro
Apr 28, 2016·The Biochemical Journal·Yangzom D BhutiaVadivel Ganapathy
Jun 22, 2016·Progress in Brain Research·S Baulac
Oct 1, 2016·International Journal of Molecular Sciences·Liufeng ZhengJian Peng
Aug 10, 2017·Journal of Molecular Neuroscience : MN·Pengfei XueZhiming Cui
Sep 22, 2017·Nature Reviews. Neuroscience·Urte Neniskyte, Cornelius T Gross
Feb 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Laura E ClarkeBen A Barres
Aug 15, 2018·International Journal of Molecular Sciences·Travis B Salisbury, Subha Arthur

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