000201441 001__ 201441
000201441 005__ 20181203023607.0
000201441 0247_ $$2doi$$a10.1002/ana.24162
000201441 022__ $$a0364-5134
000201441 02470 $$2ISI$$a000337706100013
000201441 037__ $$aARTICLE
000201441 245__ $$aCortical Interneuron Loss and Symptom Heterogeneity in Huntington Disease
000201441 260__ $$bWiley-Blackwell$$c2014$$aHoboken
000201441 269__ $$a2014
000201441 300__ $$a11
000201441 336__ $$aJournal Articles
000201441 520__ $$aObjective: The cellular basis of variable symptoms in Huntington disease (HD) is unclear. One important possibility is that degeneration of the interneurons in the cerebral cortex, which play a critical role in modulating cortical output to the basal ganglia, might play a significant role in the development of variable symptomatology in HD. This study aimed to examine whether symptom variability in HD is specifically associated with variable degeneration of cortical interneurons. Methods: We undertook a double-blind study using stereological cell counting methods to quantify the 3 major types of gamma-aminobutyric acidergic interneurons (calbindin-D28k, calretinin, parvalbumin) in 13 HD cases of variable motor/mood symptomatology and 15 matched control cases in the primary motor and anterior cingulate cortices. Results: In the primary motor cortex, there was a significant loss (57% reduction) of only calbindin interneurons (p=0.022) in HD cases dominated by motor symptoms, but no significant interneuron loss in cases with a dominant mood phenotype. In contrast, the anterior cingulate cortex showed a major significant loss in all 3 interneuron populations, with 71% loss of calbindin (p=0.001), 60% loss of calretinin (p=0.001), and 80% loss of parvalbumin interneurons (p=0.005) in HD cases with major mood disorder, and no interneuron loss was observed in cases with major motor dysfunction. Interpretation: These findings suggest that region-specific degeneration of cortical interneurons is a key component in understanding the neural basis of symptom heterogeneity in HD.
000201441 700__ $$uUniv Auckland, Dept Anat Radiol, Auckland 1, New Zealand$$aKim, Eric H.
000201441 700__ $$uUniv Auckland, Ctr Brain Res, Auckland 1, New Zealand$$aThu, Doris C. V.
000201441 700__ $$uUniv Auckland, Ctr Brain Res, Auckland 1, New Zealand$$aTippett, Lynette J.
000201441 700__ $$uUniv Otago, Dept Anat, Dunedin, New Zealand$$aOorschot, Dorothy E.
000201441 700__ $$uUniv Auckland, Ctr Brain Res, Auckland 1, New Zealand$$aHogg, Virginia M.
000201441 700__ $$uUniv Auckland, Ctr Brain Res, Auckland 1, New Zealand$$aRoxburgh, Richard
000201441 700__ $$uUniv Auckland, Ctr Brain Res, Auckland 1, New Zealand$$aSynek, Beth J.
000201441 700__ $$uUniv Auckland, Dept Anat Radiol, Auckland 1, New Zealand$$aWaldvogel, Henry J.
000201441 700__ $$uUniv Auckland, Dept Anat Radiol, Auckland 1, New Zealand$$aFaull, Richard L. M.
000201441 773__ $$j75$$tAnnals Of Neurology$$k5$$q717-727
000201441 909C0 $$xU10454$$0252449$$pBMI
000201441 909CO $$pSV$$particle$$ooai:infoscience.tind.io:201441
000201441 937__ $$aEPFL-ARTICLE-201441
000201441 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000201441 980__ $$aARTICLE