Cortical interneuron loss and symptom heterogeneity in Huntington disease. Issue 5 (13th May 2014)

• Record Type: Journal Article
• Authors: Kim, Eric H.; Thu, Doris C. V.; Tippett, Lynette J.; Oorschot, Dorothy E.; Hogg, Virginia M.; Roxburgh, Richard; Synek, Beth J.; Waldvogel, Henry J.; Faull, Richard L. M.
• Is Part Of: Annals of neurology. Volume 75:Issue 5(2014:May)
• Page Start: 717
• Page End: 727
• Publication Date: 2014-05-13
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24162
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24162-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="ana24162-sec-0002" sec-type="section"> <title>Methods</title> <p>We undertook a double‐blind study using stereological cell counting methods to quantify the 3 major types of γ‐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.</p> </sec> <sec id="ana24162-sec-0003" sec-type="section"> <title>Results</title> <p>In the primary motor cortex, there was a significant loss (57% reduction) of only calbindin interneurons (<italic>p</italic> = 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 (<italic>p</italic> = 0.001), 60% loss of calretinin (<italic>p</italic> = 0.001), and 80% loss of parvalbumin interneurons (<italic>p</italic> = 0.005) in HD cases with major mood disorder, and no interneuron loss was observed in cases with major motor dysfunction.</p> </sec> <sec id="ana24162-sec-0004" sec-type="section"> <title>Interpretation</title> <p>These findings suggest that region‐specific degeneration of cortical interneurons is a key component in understanding the neural basis of symptom heterogeneity in HD. Ann Neurol 2014;75:717–727</p> </sec> </abstract>