SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease

Neuropathology and Applied Neurobiology
B BaldoAsa Petersén

Abstract

Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin-concentrating hormone (MCH) in the LHA and of brain-derived neurotrophic factor (BDNF) in ...Continue Reading

References

Dec 9, 1991·Neuroscience Letters·J C HedreenC A Ross
Jul 1, 1990·Journal of Neuropathology and Experimental Neurology·H P KremerG T Bots
Nov 1, 1985·Journal of Neuropathology and Experimental Neurology·J P VonsattelE P Richardson
Aug 1, 1988·Pharmacology, Biochemistry, and Behavior·M A ParadaB G Hoebel
Jan 8, 1999·Experimental Neurology·G M HallidayE McCusker
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·W E LyonsL Tessarollo
Nov 5, 2004·Human Molecular Genetics·Asa PetersénPatrik Brundin
Jan 7, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ying Li, Anthony N van den Pol
Mar 29, 2005·Nature Genetics·J Alex ParkerChristian Néri
Feb 10, 2006·Human Molecular Genetics·Angela HodgesRuth Luthi-Carter
Feb 14, 2006·Molecular Aspects of Medicine·Simone Fleige, Michael W Pfaffl
Oct 19, 2006·Brain Research·Ana D StanCarol A Tamminga
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thaddeus J UngerMaribel Rios
Oct 3, 2008·Brain : a Journal of Neurology·Marios PolitisPaola Piccini
Oct 3, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Giorgio RamadoriRoberto Coppari
Dec 17, 2009·Journal of Neuropathology and Experimental Neurology·Pascal F DurrenbergerRichard Reynolds
Apr 9, 2010·Brain : a Journal of Neurology·Doris C V ThuRichard L M Faull
Apr 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ruth Luthi-CarterAleksey G Kazantsev
Jun 16, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·O FroyR Miskin
Jul 28, 2010·Human Molecular Genetics·Jinho KimRobert J Ferrante
Jul 30, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Akiko SatohShin-ichiro Imai
Aug 5, 2010·Neurobiology of Disease·Charlotte SonesonUNKNOWN Huntington Study Group PREDICT-HD investigators
Dec 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Salvatore FuscoGiovambattista Pani
Sep 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·J Alex ParkerChristian Neri
Dec 4, 2012·Cell Reports·Vanita ChopraAleksey G Kazantsev
Feb 19, 2013·EMBO Molecular Medicine·Gizem Donmez, Tiago F Outeiro
Jul 16, 2013·Nature Neuroscience·Matthew M DobbinLi-Huei Tsai
Jul 28, 2013·Frontiers in Aging Neuroscience·Wenzhen Duan

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Citations

Oct 9, 2019·Journal of Huntington's Disease·Rachel Y CheongÅsa Petersén
Dec 18, 2019·Open Medicine·Zheng Huang, Hang Xu
Oct 31, 2018·Frontiers in Endocrinology·Birsen Elibol, Ulkan Kilic
Dec 18, 2020·Neuropathology and Applied Neurobiology·Rachel Y CheongÅsa Petersén
Apr 4, 2021·International Journal of Molecular Sciences·Noemi Sola-SevillaElena Puerta
Aug 28, 2021·Acta Neuropathologica·Sanaz GaberyÅsa Petersén
Aug 28, 2021·International Journal of Molecular Sciences·Amy KimJoana Gil-Mohapel

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