Friedreich ataxia: Developmental failure of the dorsal root entry zone

Arnulf H. Koeppen, Alyssa B. Becker, Jiang Qian, Benjamin B. Gelman, Joseph E. Mazurkiewicz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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, alphadystroglycan, 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.

Original languageEnglish (US)
Pages (from-to)969-977
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number11
DOIs
StatePublished - 2017

Keywords

  • Boundary cap
  • Dorsal root entry zone
  • Dorsal root ganglion
  • Friedreich ataxia
  • Glia
  • Schwann cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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