Friedreich Ataxia: Developmental Failure of the Dorsal Root Entry Zone.

TitleFriedreich Ataxia: Developmental Failure of the Dorsal Root Entry Zone.
Publication TypeJournal Article
Year of Publication2017
AuthorsKoeppen, AH, Becker, AB, Qian, J, Gelman, BB, Mazurkiewicz, JE
JournalJ Neuropathol Exp Neurol
Date Published2017 Nov 01
KeywordsAdolescent, Adult, Aged, Child, Female, Friedreich Ataxia, Ganglia, Spinal, Humans, Male, Middle Aged, Spinal Cord, Spinal Nerve Roots, Young Adult

Dorsal root ganglia, dorsal roots (DR), and dorsal root entry zones (DREZ) are vulnerable to frataxin deficiency in Friedreich ataxia (FA). A previously unrecognized abnormality is the intrusion of astroglial tissue into DR. Segments of formalin-fixed upper lumbar spinal cord of 13 homozygous and 2 compound heterozygous FA patients were sectioned longitudinally to represent DREZ and stained for glial fibrillary acidic protein (GFAP), S100, vimentin, the central nervous system (CNS)-specific myelin protein proteolipid protein, the peripheral nervous system (PNS) myelin proteins PMP-22 and P0, and the Schwann cell proteins laminin, alpha-dystroglycan, and periaxin. Normal DREZ showed short, sharply demarcated, dome-like extensions of CNS tissue into DR. The Schwann cell-related proteins formed tight caps around these domes. In FA, GFAP-, S100-, and vimentin-reactive CNS tissue extended across DREZ and into DR over much longer distances by breaching the CNS-PNS barrier. The transition between PNS and CNS myelin proteins was disorganized. During development, neural-crest derived boundary cap cells provide guidance to dorsal root ganglia axons growing into the dorsal spinal cord and at the same time block the inappropriate intrusion of CNS glia into DR. It is likely that frataxin is required during a critical period of permissive (axons) and nonpermissive (astroglia) border-control.

Alternate JournalJ Neuropathol Exp Neurol
PubMed ID29044418
PubMed Central IDPMC6440497
Grant ListU24 MH100930 / MH / NIMH NIH HHS / United States