Abstract
Huntington Disease (HD) is a devastating neurological disorder characterized by progressive deterioration of psychiatric, motor, and cognitive function. Purkinje cells (PCs), the output neurons of the cerebellar cortex, have been found to be vulnerable in multiple CAG repeat disorders, but little is known about the involvement of PC dysfunction in HD. To investigate possible PC abnormalities, we performed quantitative real time PCR, Western blot analysis, and immunohistochemistry experiments to explore the changes in PC markers in the R6/2 mouse model of severe HD. There were reductions in the transcript and protein levels of the calcium-binding proteins parvalbumin and calbindin, as well as the enzyme glutamic acid decarboxylase 67. Immunohistochemistry supported these results, with the most substantial changes occurring in the PC layer. To determine whether the reductions in PC marker expression were due to cell loss, we performed stereology on both presymptomatic and end-stage R6/2 mice. Stereological counts indicated a significant reduction in PC number by end-stage but no change in presymptomatic animals (4 weeks of age). To assess cellular function prior to cell loss and symptom onset, we measured spontaneous firing in PC...Continue Reading
References
Jul 1, 1991·Journal of Neuropathology and Experimental Neurology·A H Koeppen
Aug 14, 1990·Neuroscience Letters·J LitwakG A Oltmans
Oct 1, 1985·Neurology·W C Koller, J Trimble
Jul 1, 1996·Neurology·P J VigS H Subramony
Jan 27, 1998·Neurology·P J VigZ Qin
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J H ChaA B Young
May 2, 2001·Human Molecular Genetics·H AdachiG Sobue
Nov 13, 2001·Brain Research Bulletin·A J MortonJ M Edwardson
Aug 8, 2002·Human Molecular Genetics·Ruth Luthi-CarterJames M Olson
May 29, 2003·Neurology·H D RosasJ M Goldstein
Jul 26, 2003·The Cerebellum·Beat SchwallerSerge Schiffmann
Sep 29, 2004·Neurology·C Fennema-NotestineT L Jernigan
Oct 16, 2004·Nature·Montserrat ArrasateSteven Finkbeiner
May 18, 2005·The Cerebellum·Arnulf H Koeppen
Feb 14, 2006·Nature Neuroscience·Joy T WalterKamran Khodakhah
Apr 20, 2006·Arquivos de neuro-psiquiatria·Heloísa H RuoccoFernando Cendes
Mar 14, 2007·Brain Research Bulletin·Jeremy M Van RaamsdonkMichael R Hayden
Jul 7, 2007·Journal of Neurology, Neurosurgery, and Psychiatry·H H RuoccoF Cendes
Oct 22, 2008·Neurobiology of Disease·S J SawiakT A Carpenter
Mar 3, 2009·American Journal of Medical Genetics. Part a·Satoru SakazumeHirofumi Ohashi
Jul 28, 2009·NeuroImage·Jörg B SchulzTill-Karsten Hauser
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andreea C BostanPeter L Strick
Sep 3, 2010·Neuropsychology Review·Andreea C Bostan, Peter L Strick
Jan 7, 2011·PloS One·Patrick Lajoie, Erik Lee Snapp
Feb 8, 2011·Nature Neuroscience·D Paola CalderonKamran Khodakhah
Mar 18, 2011·American Journal of Medical Genetics. Part a·Gaël NicolasLucie Guyant-Maréchal
Apr 5, 2011·Neurobiology of Disease·Jeffrey B CarrollMichael R Hayden
Jun 16, 2011·BioFactors·Marta GiacomelloRaffaele Lopreiato
Nov 19, 2011·Genetics·Kurt R WeissJ Troy Littleton
Citations
May 3, 2014·The Cerebellum·Parminder J S VigMaripar E Lopez
Jul 6, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ravi Chopra, Vikram G Shakkottai
Feb 20, 2013·Brain Research·Hsin Hsien YehDavid M A Mann
Oct 11, 2014·Neurobiology of Disease·Pawel M SwitonskiMaciej Figiel
Nov 28, 2015·Stem Cell Research·Aynun N BegumYiling Hong
Jul 16, 2014·Neurobiology of Aging·Maarten OomsCindy Casteels
Dec 1, 2012·Experimental Neurology·S E DoughertyR M Cowell
Sep 16, 2014·Future Neurology·Ravi Chopra, Vikram G Shakkottai
Apr 9, 2015·Brain Structure & Function·A K Samhan-AriasC Gutierrez-Merino
Aug 14, 2013·Experimental Neurology·Elisa J CopsRobert L Medcalf
Jan 23, 2015·Frontiers in Cellular Neuroscience·Elizabeth K LucasRita M Cowell
Aug 18, 2016·The Journal of Physiology·Sriram JayabalAlanna J Watt
Sep 5, 2018·Journal of the American Veterinary Medical Association·Lorenzo MariLuisa De Risio
Feb 9, 2020·Acta Neuropathologica Communications·Gabriel Crevier-SorboAbbas F Sadikot
Apr 23, 2020·Frontiers in Neuroscience·Polina A EgorovaIlya B Bezprozvanny
Aug 4, 2018·Proteomes·Marcia RoySeth G N Grant
Jul 1, 2019·Journal of Huntington's Disease·Joakim Iver PostLise Sofie H Nissen-Meyer
Nov 29, 2020·Cell Calcium·Polina A EgorovaIlya B Bezprozvanny
Oct 4, 2019·Redox Biology·Margaret M LoniewskaPeter G Wells
Feb 13, 2021·Cells·Laura J McMeekinRita M Cowell
Jun 20, 2020·Neuroscience·Anna A CookAlanna J Watt