Cerebellar contribution to the cognitive alterations in SCA1: evidence from mouse models.

Human Molecular Genetics
Melissa AsherMarija Cvetanovic


Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine (Q) encoding CAG repeats in the gene Ataxin-1 (ATXN1). Although motor and balance deficits are the core symptoms of SCA1, cognitive decline is also commonly observed in patients. While mutant ATXN1 is expressed throughout the brain, pathological findings reveal severe atrophy of cerebellar cortex in SCA1 patients. The cerebellum has recently been implicated in diverse cognitive functions, yet to what extent cerebellar neurodegeneration contributes to cognitive alterations in SCA1 remains poorly understood. Much of our understanding of the mechanisms underlying pathogenesis of motor symptoms in SCA1 comes from mouse models. Reasoning that mouse models could similarly offer important insights into the mechanisms of cognitive alterations in SCA1, we tested cognition in several mouse lines using Barnes maze and fear conditioning. We confirmed cognitive deficits in Atxn1154Q/2Q knock-in mice with brain-wide expression of mutant ATXN1 and in ATXN1 null mice. We found that shorter polyQ length and haploinsufficiency of ATXN1 do not cause significant cognitive deficits. Finally, ATXN1[82Q ] transgenic mice-with cerebellum...Continue Reading


Aug 1, 1993·Neurology·I M AppollonioM Hallett
Jul 1, 1996·Journal of Neurology·S N IllarioshkinI A Ivanova-Smolenskaya
May 13, 1998·Brain : a Journal of Neurology·J D Schmahmann, J C Sherman
May 13, 1998·Brain : a Journal of Neurology·T KlockgetherJ Dichgans
Mar 2, 1999·Brain : a Journal of Neurology·J DrepperH C Diener
Dec 1, 1996·Journal of Neurogenetics·N Hadj-SahraouiJ Mariani
Jan 3, 2001·Brain : a Journal of Neurology·M AllinR M Murray
Mar 17, 2001·Nature Reviews. Neuroscience·J F Gusella, M E MacDonald
Jun 25, 2002·Trends in Neurosciences·Verity J Brown, Eric M Bowman
Feb 8, 2003·Journal of Neurology·K BürkJ Dichgans
Jun 14, 2006·Neurology·T Schmitz-HübschRoberto Fancellu
Oct 21, 2006·Lancet Neurology·Sarah-Michelle OrtonUNKNOWN Canadian Collaborative Study Group
Sep 18, 2007·Brain : a Journal of Neurology·Alessandro TavanoRenato Borgatti
Apr 18, 2008·The Cerebellum·Shannon L Dean, Margaret M McCarthy
Oct 7, 2008·NeuroImage·Catherine J Stoodley, Jeremy D Schmahmann
Oct 30, 2008·The Journal of Biological Chemistry·Huda Y Zoghbi, Harry T Orr
Nov 11, 2008·Behavioural Brain Research·F E HarrisonM P McDonald
Apr 30, 2009·Seminars in Reproductive Medicine·Candice M BrownPhyllis M Wise
Jun 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erin L Rich, Matthew Shapiro
Jun 23, 2009·Cortex; a Journal Devoted to the Study of the Nervous System and Behavior·Mario Manto, Thomas Lorivel
Jun 27, 2009·Annual Review of Neuroscience·Peter L StrickJulie A Fiez
Feb 16, 2010·Cortex; a Journal Devoted to the Study of the Nervous System and Behavior·Catherine J Stoodley, Jeremy D Schmahmann
Mar 24, 2010·Journal of Alzheimer's Disease : JAD·Karolien BettensKristel Sleegers
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andreea C BostanPeter L Strick
Jan 27, 2011·Autism Research : Official Journal of the International Society for Autism Research·Corinne M SpencerRichard Paylor
Feb 9, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Thais S RizziDanielle Posthuma
Sep 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Keith A CoffmanPeter L Strick
Nov 1, 2011·Brain : a Journal of Neurology·Anna M TedescoMaria G Leggio
Feb 9, 2012·Neuropathology and Applied Neurobiology·U RübT Deller

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