Early abnormalities in sciatic nerve function and structure in a rat model of Charcot-Marie-Tooth type 1A disease

Marina Grandis, Massimo Leandri, Tiziana Vigo, Michele Cilli, Michael W. Sereda, Gianfranco Gherardi, Luana Benedetti, Gianluigi Mancardi, Michele Abbruzzese, Klaus Armin Nave, Lucilla Nobbio, Angelo Schenone

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We investigated early peripheral nervous system impairment in PMP22-transgenic rats ("CMT rat"), an established animal model for Charcot-Marie-Tooth disease 1A, at postnatal day 30 (P30), when the clinical phenotype is not yet apparent. Hemizygous CMT1A rats and wildtype littermates were studied by means of behavioral examination, electrophysiology, molecular biology, and light microscopy analysis. Behavioral studies only showed, a mild, but significant, decrease in toe spread 1-5, suggesting a weakness of distal foot muscles in CMT1A rats compared with normal littermates. Nerve conduction studies disclosed a severe slowing in motor conduction velocity, a temporal dispersion and a dramatic decrease of amplitude of motor waves in P30 transgenic animals. Coherently with a demyelinating process, affected nerves showed a significant thinning of myelin. Interestingly, axonal diameter and area were unchanged, but expression of non-phosphorylated neurofilaments was increased in CMT1A rats compared with normal controls. Our results confirm the fidelity of this animal model to human disease. Similarly, in young CMT1A patients, the MCV is significantly reduced and the muscle weakness is confined to distal segments, whereas morphological and morphometrical signs of axonal atrophy are absent. However, the presence of a molecular and functional damage of the axons suggests that this may be the correct moment to start neuroprotective therapies.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalExperimental Neurology
Volume190
Issue number1
DOIs
Publication statusPublished - Nov 2004

Fingerprint

Charcot-Marie-Tooth Disease
Sciatic Nerve
Animal Models
Transgenic Rats
Genetically Modified Animals
Intermediate Filaments
Electrophysiology
Neural Conduction
Muscle Weakness
Peripheral Nervous System
Toes
Myelin Sheath
Atrophy
Axons
Foot
Molecular Biology
Microscopy
Phenotype
Light
Muscles

Keywords

  • Axonal atrophy
  • Charcot-Marie-Tooth type 1A
  • Demyelination
  • Experimental neurophysiology
  • Footprint analysis
  • Morphometry
  • Neurofilaments
  • Schwann cells
  • Sciatic nerve
  • Transgenic animals

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Early abnormalities in sciatic nerve function and structure in a rat model of Charcot-Marie-Tooth type 1A disease. / Grandis, Marina; Leandri, Massimo; Vigo, Tiziana; Cilli, Michele; Sereda, Michael W.; Gherardi, Gianfranco; Benedetti, Luana; Mancardi, Gianluigi; Abbruzzese, Michele; Nave, Klaus Armin; Nobbio, Lucilla; Schenone, Angelo.

In: Experimental Neurology, Vol. 190, No. 1, 11.2004, p. 213-223.

Research output: Contribution to journalArticle

Grandis, M, Leandri, M, Vigo, T, Cilli, M, Sereda, MW, Gherardi, G, Benedetti, L, Mancardi, G, Abbruzzese, M, Nave, KA, Nobbio, L & Schenone, A 2004, 'Early abnormalities in sciatic nerve function and structure in a rat model of Charcot-Marie-Tooth type 1A disease', Experimental Neurology, vol. 190, no. 1, pp. 213-223. https://doi.org/10.1016/j.expneurol.2004.07.008
Grandis, Marina ; Leandri, Massimo ; Vigo, Tiziana ; Cilli, Michele ; Sereda, Michael W. ; Gherardi, Gianfranco ; Benedetti, Luana ; Mancardi, Gianluigi ; Abbruzzese, Michele ; Nave, Klaus Armin ; Nobbio, Lucilla ; Schenone, Angelo. / Early abnormalities in sciatic nerve function and structure in a rat model of Charcot-Marie-Tooth type 1A disease. In: Experimental Neurology. 2004 ; Vol. 190, No. 1. pp. 213-223.
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