In:
Movement Disorders, Wiley, Vol. 28, No. 12 ( 2013-10), p. 1691-1699
Abstract:
Although dystonia represents a major source of motor disability in Huntington's disease (HD), its pathophysiology remains unknown. Because recent animal studies indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause dystonia, we investigated if loss of PARV+ striatal interneurons occurs during human HD progression, and thus might contribute to dystonia in HD. We used immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for disease‐related striatal atrophy by expressing PARV+ interneuron counts in ratio to interneurons co‐containing somatostatin and neuropeptide Y (whose numbers are unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced to less than 26% of normal abundance in rostral caudate. In putamen rostral to the level of globus pallidus, loss of PARV+ interneurons was more gradual, not dropping off to less than 20% of control until grade 2. Loss of PARV+ interneurons was even more gradual in motor putamen at globus pallidus levels, with no loss at grade 1, and steady grade‐wise decline thereafter. A large decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing disease grade, with regional variation in the loss per grade. Given the findings of animal studies and the grade‐wise loss of PARV+ striatal interneurons in motor striatum in parallel with the grade‐wise appearance and worsening of dystonia, our results raise the possibility that loss of PARV+ striatal interneurons is a contributor to dystonia in HD.
Type of Medium:
Online Resource
ISSN:
0885-3185
,
1531-8257
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2041249-6
