HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity

Human Molecular Genetics
Virginia B MattisClive N Svendsen

Abstract

Huntington's disease (HD) is a fatal neurodegenerative disease, caused by expansion of polyglutamine repeats in the Huntingtin gene, with longer expansions leading to earlier ages of onset. The HD iPSC Consortium has recently reported a new in vitro model of HD based on the generation of induced pluripotent stem cells (iPSCs) from HD patients and controls. The current study has furthered the disease in a dish model of HD by generating new non-integrating HD and control iPSC lines. Both HD and control iPSC lines can be efficiently differentiated into neurons/glia; however, the HD-derived cells maintained a significantly greater number of nestin-expressing neural progenitor cells compared with control cells. This cell population showed enhanced vulnerability to brain-derived neurotrophic factor (BDNF) withdrawal in the juvenile-onset HD (JHD) lines, which appeared to be CAG repeat-dependent and mediated by the loss of signaling from the TrkB receptor. It was postulated that this increased death following BDNF withdrawal may be due to glutamate toxicity, as the N-methyl-d-aspartate (NMDA) receptor subunit NR2B was up-regulated in the cultures. Indeed, blocking glutamate signaling, not just through the NMDA but also mGlu and AMPA/K...Continue Reading

References

Jul 1, 1990·Trends in Neurosciences·M DiFiglia
Mar 29, 1989·European Journal of Pharmacology·J KornhuberP Riederer
Jan 1, 1985·Annals of the New York Academy of Sciences·P Rakic
Feb 25, 1998·Brain Research. Developmental Brain Research·A F SadikotR Sasseville
Jul 17, 1998·Frontiers in Bioscience : a Journal and Virtual Library·M Palmada, J J Centelles
Apr 27, 1999·Journal of Neurochemistry·N ChenL A Raymond
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KazantsevD Housman
Oct 13, 1999·Brain Research·S Sahin KayaM Chopp
May 29, 2000·Brain Research·I FerrerT Ribalta
Nov 25, 2000·Human Molecular Genetics·F TrettelM E MacDonald
Aug 29, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·V BrunoF Nicoletti
Aug 8, 2002·Human Molecular Genetics·Simonetta SipioneElena Cattaneo
Jul 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maurice A CurtisRichard L M Faull
Sep 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katia VaraniElena Cattaneo
Sep 3, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Josep M CanalsJordi Alberch
Sep 7, 2004·Annals of Neurology·Hyemyung SeoOle Isacson
Dec 2, 2004·Neurobiology of Disease·Paolo GuidettiRobert Schwarcz
Feb 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mikko SairanenEero Castrén
Mar 12, 2005·Journal of the Neurological Sciences·Andrius Baskys, Morten Blaabjerg
Jun 14, 2005·Neurobiology of Disease·Joana M A C GilAsa Petersén
Aug 11, 2005·The Journal of Biological Chemistry·Pieter H AnborghStephen S G Ferguson
Sep 24, 2005·Annals of the New York Academy of Sciences·Andrius BaskysIldar Bayazitov
Nov 3, 2005·The European Journal of Neuroscience·Helen E GroteAnthony J Hannan
Dec 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wendy PhillipsRoger A Barker
Apr 18, 2006·Journal of the Neurological Sciences·Yuji MizunoKoichi Okamoto
Jun 22, 2006·Current Topics in Medicinal Chemistry·Katalin Schlett
Jul 20, 2006·The European Journal of Neuroscience·Masatoshi SuzukiClive N Svendsen
Jul 6, 2007·The European Journal of Neuroscience·Rebecca A HenryBronwen Connor

❮ Previous
Next ❯

Citations

Jan 31, 2016·Experimental Neurology·Monika M Golas, Bjoern Sander
Dec 15, 2015·Molecular and Cellular Neurosciences·Alison E MungenastLi-Huei Tsai
Oct 3, 2015·Brain Research·Ningzhe ZhangLisa M Ellerby
Oct 16, 2015·Brain Research·Virginia B Mattis, Clive N Svendsen
Jun 5, 2016·Cellular and Molecular Life Sciences : CMLS·Edyta JaworskaWlodzimierz J Krzyzosiak
Feb 19, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Megan Bowers, Sebastian Jessberger
Jul 4, 2016·Journal of Huntington's Disease·Adelaide Tousley, Kimberly B Kegel-Gleason
Apr 6, 2018·Acta Pharmacologica Sinica·Rachel J Harding, Yu-Feng Tong
Jan 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·P ConfortiE Cattaneo
Nov 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Cristina CariuloAndrea Caricasole
Oct 26, 2018·Human Molecular Genetics·Robert GooldSarah J Tabrizi
Jul 30, 2019·Journal of Neuroscience Research·Carlos CepedaHarry V Vinters
Sep 19, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jordi Creus-Muncunill, Michelle E Ehrlich
Oct 27, 2017·Frontiers in Neuroscience·Hansjörg RindtVirginia B Mattis
May 8, 2019·The Journal of Clinical Investigation·Elena VezzoliChiara Zuccato
May 17, 2017·Current Protocols in Stem Cell Biology·Aslam Abbasi Akhtar, Joshua J Breunig
Mar 12, 2019·Journal of Huntington's Disease·Nicolas ArbezChristopher A Ross
Oct 20, 2020·Frontiers in Cell and Developmental Biology·Carla LopesAna Cristina Carvalho Rego
Apr 9, 2020·Molecular Cell·Arun ThiruvalluvanHarm H Kampinga

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.