title: Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia.
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.
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Reiner
authors.forename: Evan
authors.initials: E
authors.lastname: Shelby
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.forename: Zena
authors.initials: Z
authors.lastname: Demarch
authors.forename: Yunping
authors.initials: Y
authors.lastname: Deng
authors.forename: Natalie Hart
authors.initials: NH
authors.lastname: Guley
authors.forename: Virginia
authors.initials: V
authors.lastname: Hogg
authors.forename: Richard
authors.initials: R
authors.lastname: Roxburgh
authors.forename: Lynette J
authors.initials: LJ
authors.lastname: Tippett
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Waldvogel
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D004421:Dystonia / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010320:Parvalbumins / Q000378:metabolism*
chemical_list: D010320:Parvalbumins
keywords: Huntington's disease; dystonia; parvalbuminergic interneurons; striatum