Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons.

Proceedings of the National Academy of Sciences of the United States of America
Jens BrodbeckYadong Huang

Abstract

Convergent evidence has revealed an association between insulin resistance and Alzheimer's disease (AD), and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, an insulin sensitizer and mitochondrial activator, improves cognition in patients with early or mild-to-moderate AD. Apolipoprotein (apo) E4, a major genetic risk factor for AD, exerts neuropathological effects through multiple pathways, including impairment of dendritic spine structure and mitochondrial function. Here we show that rosiglitazone significantly increased dendritic spine density in a dose-dependent manner in cultured primary cortical rat neurons. This effect was abolished by the PPAR-gamma-specific antagonist, GW9662, suggesting that rosiglitazone exerts this effect by activating the PPAR-gamma pathway. Furthermore, the C-terminal-truncated fragment of apoE4 significantly decreased dendritic spine density. Rosiglitazone rescued this detrimental effect. Thus, rosiglitazone might improve cognition in AD patients by increasing dendritic spine density.

References

Feb 15, 1997·American Journal of Epidemiology·C L LeibsonP J Palumbo
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·J RaberL Mucke
May 5, 1999·Diabetic Medicine : a Journal of the British Diabetic Association·C Day
Feb 24, 2001·Annals of the New York Academy of Sciences·S HoyerR Schliebs
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y HuangR W Mahley
Oct 3, 2001·American Journal of Epidemiology·J A LuchsingerR Mayeux
Sep 17, 2002·The American Journal of Cardiology·Barry J Goldstein
Oct 3, 2002·Nature Reviews. Immunology·Raymond A Daynes, Dallas C Jones
Jan 17, 2003·Molecular and Cellular Biology·Leanne Wilson-FritchSilvia Corvera
Feb 8, 2003·Annual Review of Neuroscience·Richard Mayeux
Aug 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Faith M HarrisYadong Huang
Nov 6, 2003·Journal of Chemical Neuroanatomy·Upinder S Bhalla
Mar 12, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Walter J BrechtYadong Huang
May 19, 2004·Archives of Neurology·Zoe ArvanitakisDavid A Bennett
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Priya MohantyParesh Dandona
Mar 12, 2005·Journal of the Neurological Sciences·Ofir LeviDaniel M Michaelson
Mar 30, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Patrick G Sullivan, Maile R Brown
Jul 21, 2005·Annual Review of Neuroscience·Christian Dillon, Yukiko Goda
Nov 16, 2005·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·G Stennis WatsonSuzanne Craft
Dec 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shengjun ChangYadong Huang
Jan 25, 2006·Neurology·Yadong Huang
Feb 1, 2006·The Pharmacogenomics Journal·M E RisnerUNKNOWN Rosiglitazone in Alzheimer's Disease Study Group
Mar 7, 2006·Experimental Neurology·Ward A PedersenGleb R Haynatzki
Mar 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Robert W MahleyYadong Huang
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qin XuYadong Huang
Oct 21, 2006·Biochemical and Biophysical Research Communications·Shang-Der ChenYao-Chung Chuang

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Citations

Jun 17, 2010·Neurotoxicity Research·Peter RiedererEdna Grünblatt
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Gary LandrethMichael Heneka
Jun 7, 2013·PloS One·Rodrigo A QuintanillaNibaldo C Inestrosa
Mar 12, 2013·TheScientificWorldJournal·Benoît Leclerc, Abedelnasser Abulrob
Sep 24, 2014·PPAR Research·Rodrigo A QuintanillaFabián A Cabezas-Opazo
Dec 25, 2008·Journal of Lipid Research·Robert W MahleyYadong Huang
Nov 19, 2009·Drug Design, Development and Therapy·Gerald F DaviesTroy A A Harkness
Dec 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sonya B DumanisHyang-Sook Hoe
Sep 28, 2010·American Journal of Respiratory Cell and Molecular Biology·Ming ZhuStephanie A Shore
May 15, 2015·The American Journal of the Medical Sciences·Lina MaJingyan Zhang
Dec 3, 2010·The EPMA Journal·Iris GrossmanAllen D Roses
May 12, 2009·Neuroscience Letters·Gianluca MiglioRoberto Fantozzi
May 13, 2008·Neuroscience and Biobehavioral Reviews·Borja García-BuenoJuan C Leza
Mar 16, 2012·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Phebe VerbruggheLuba Kalaydjieva
Nov 25, 2014·Expert Opinion on Therapeutic Patents·Ichiro Takada, Makoto Makishima
Jul 3, 2015·Frontiers in Neuroscience·Gaurav BedseTommaso Cassano
Jul 8, 2008·PPAR Research·Paul D DrewMichael K Racke
Feb 26, 2014·Current Opinion in Pharmacology·Allen D RosesStephen K Brannan
Sep 1, 2014·Neurobiology of Disease·Yadong Huang, Robert W Mahley
Dec 12, 2012·Neuron·Robert W Mahley, Yadong Huang
Nov 22, 2008·Biochimica Et Biophysica Acta·Shayna A WrightenLawrence P Reagan
Aug 31, 2010·The International Journal of Neuropsychopharmacology·Borja García-BuenoJuan C Leza
May 8, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Allen RosesMichael Lutz
Jun 10, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Robert W Mahley
Sep 21, 2016·Journal of Molecular Neuroscience : MN·Laura Mahoney-SanchezScott Ayton

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