Viral vector mediated expression of mutant huntingtin in the dorsal raphe produces disease-related neuropathology but not depressive-like behaviors in wildtype mice

Brain Research
Mark R PitzerJodi L McBride

Abstract

Huntington׳s disease (HD) is a neurodegenerative disorder caused by a mutation in the HTT gene (mHTT) encoding the protein huntingtin. An expansion in the gene׳s CAG repeat length renders a misfolded, dysfunctional protein with an abnormally long glutamine (Q) stretch at the N terminus that often incorporates into inclusion bodies and leads to neurodegeneration in many regions of the brain. HD is characterized by motor and cognitive decline as well as mood disorders, with depression being particularly common. Approximately 40% of the HD population suffers from depressive symptoms. Because these symptoms often manifest a decade or more prior to the knowledge that the person is at risk for the disease, a portion of the early depression in HD appears to be a consequence of the pathology arising from expression of the mutant gene. While the depression in HD patients is often treated with serotonin agonists, there is scant experimental evidence that the depression in HD responds well to these serotonin treatments or in a similar manner to how non-HD depression tends to respond. Additionally, at very early sub-threshold depression levels, abnormal changes in several neuronal populations are already detectable in HD patients, suggesti...Continue Reading

References

Jul 1, 1976·Archives of General Psychiatry·B ShopsinS Gershon
Jan 1, 1990·The Journal of Nervous and Mental Disease·A BurnsM Folstein
Dec 1, 1974·The Journal of Pharmacy and Pharmacology·E FriedmanS Gershon
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·M F PerutzJ T Finch
Sep 1, 1997·Physiology & Behavior·J A Van der HeydenB Olivier
Aug 7, 1998·Biological Psychiatry·I Lucki
Mar 9, 2002·Psychological Medicine·B BaumannB Bogerts
Aug 23, 2005·Biological Psychiatry·Jane S PaulsenPeg C Nopoulos
Dec 21, 2006·Journal of Neurology, Neurosurgery, and Psychiatry·Camille L JulienDavid Craufurd
Feb 24, 2007·Brain Research Reviews·Kimmo A MichelsenHarry W M Steinbusch
May 8, 2007·Biological Psychiatry·Kevin DuffUNKNOWN Predict-HD Investigators of the Huntington Study Group
Dec 22, 2007·Journal of Neurology, Neurosurgery, and Psychiatry·J S PaulsenUNKNOWN Predict-HD Investigators and Coordinators of the Huntington Study Group
Dec 25, 2007·Physiology & Behavior·Anita J BechtholtIrwin Lucki
Feb 23, 2008·General Hospital Psychiatry·Elisabeth M KingmaRaymund A C Roos
Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nicholas R FranichDeborah Young
Apr 9, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Octavian R Adam, Joseph Jankovic
Feb 3, 2009·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Lise GutknechtKlaus-Peter Lesch
Dec 10, 2009·International Clinical Psychopharmacology·Anna K HollRaphael M Bonelli
Jan 29, 2011·Brain Research Bulletin·Nurgul Carkaci-SalliKent E Vrana
Apr 13, 2011·PloS One·Fanny MochelRaphael Schiffmann
May 11, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Nicola Z HobbsRachael I Scahill
May 25, 2011·Psychiatry Research·Heather H WetzelUNKNOWN Huntington Study Group
Jul 2, 2011·British Journal of Pharmacology·Thibault RenoirAnthony J Hannan
Jul 26, 2012·Neural Plasticity·Mark I RansomeAnthony J Hannan

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Citations

Jul 26, 2019·Neurobiology of Disease·Udaiyappan JanakiramanMark A Nelson

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