Dorsal root ganglia in Friedreich ataxia: the critical role of - - PowerPoint PPT Presentation

▶

Mar 28, 2024 254 likes •399 views

Dorsal root ganglia in Friedreich ataxia: the critical role of satellite cells Arnulf H. Koeppen, R. Liane Ramirez, Alyssa B. Becker, and Joseph E. Mazurkiewicz Albany, N.Y., USA Friedreich ataxia (FRDA) Definition: An autosomal recessive

SLIDE 1

Dorsal root ganglia in Friedreich ataxia: the critical role of satellite cells

Arnulf H. Koeppen, R. Liane Ramirez, Alyssa B. Becker, and Joseph E. Mazurkiewicz

Albany, N.Y., USA

SLIDE 2

Friedreich ataxia (FRDA) Definition: An autosomal recessive ataxia due to homozygous guanine-adenine-adenine trinucleotide repeat expansion in intron 1 of the frataxin (FXN) gene

n chromosome 9q21.11, causing impaired transcription

and lack of a small mitochondrial protein, frataxin. Prevalence: 1:40,000 – 1:140,000 (Western European peoples); total in USA, 6,000-10,000 Disease targets: Motor cortex; dentate nucleus; dorsal root ganglia (DRG); sensory nerve; heart; β-cells of the pancreas This study: DRG of Friedreich ataxia (15 cases); normal controls (12) Nikolaus Friedreich 1825-1882

SLIDE 3

Normal Normal, class-III-β-tubulin FRDA, class-III-β-tubulin FRDA

SLIDE 4

Normal, laminin 2 FRDA, laminin 2

SLIDE 5

Normal, glutamine synthetase FRDA, glutamine synthetase FRDA, GFAP Normal, GFAP

SLIDE 6

Normal, connexin 43 FRDA, connexin 43 Normal, S100 FRDA, S100α

SLIDE 7

Normal S100 Normal connexin 43 Normal merged FRDA S100 FRDA connexin 43 FRDA merged

SLIDE 8

Normal, mGluR2/3 FRDA, mGluR2/3 Normal, mGluR1α FRDA, mGluR1α

SLIDE 9

Normal, EAAT1 FRDA, EAAT1 Normal, Kir4.1 FRDA, Kir4.1

SLIDE 10

Normal, IBA1 FRDA, IBA1 Normal, CD68 FRDA, CD68

SLIDE 11

Normal S100/IBA1 FRDA S100/IBA1

SLIDE 12

Normal, frataxin FRDA, frataxin Normal, ATP5B FRDA, ATP5B

SLIDE 13

Key observations: (1)Hypertrophy and hyperplasia of satellite cells expressing glutamine synthetase, S100, the gap junction protein connexin 43, basement membrane material (laminin-2), GFAP, EAAT1, Kir4.1, frataxin, and ATP5B (2)Infiltration of DRG by monocytes and neuronal invasion (IBA1 and CD68) Conclusions The traditional interpretation that FRDA causes “atrophy” of DRG neurons must be modified. Lack of frataxin causes generalized morphological abnormalities of satellite cells, disturbing their trophic interaction with neurons. Neuronal destruction is due to inflammatory infiltration and invasion by monocytes rather than “atrophy”.

Acknowledgments Supported by NIH and Friedreich’s Ataxia Research Alliance