Vacuolization correlates with spin-spin relaxation time in motor brainstem nuclei and behavioural tests in the transgenic G93A-SOD1 mouse model of ALS

Selina Bucher, Kerstin E. Braunstein, Heiko G. Niessen, Thomas Kaulisch, Michael Neumaier, Tobias M. Boeckers, Detlef Stiller, Albert C. Ludolph

Research output: Contribution to journalArticle

Abstract

In recent years, magnetic resonance imaging (MRI) has emerged as a preferred tool for the diagnosis of amyotrophic lateral sclerosis (ALS) in humans. A widely used animal model for human ALS is the G93A-superoxide dismutase 1 (G93A-SOD1) transgenic mouse model. However, the mechanisms for the selective degeneration of motor neurons in the brainstem and spinal cord are still uncertain. In our study, we applied MRI at 4.7 Tesla to non-invasively evaluate pathological alterations in the brainstem of this animal model and to follow the progression of the disease. Extending previous investigation, we used the relaxation parameter T2 as a suitable measure for the progression of ALS, and evaluated the potential agreement with histological evaluation and behavioural data of open-field tests. In the brainstem of G93A-SOD1 mice, T2 values were significantly increased in the motor nuclei Nc. V, Nc. VII and Nc. XII, as early as Day 80, i.e. before the average disease onset at about Day 90. Moreover, this increase is associated with a progressive development of vacuoles in the brainstem motor nuclei and a significantly decreased performance in behavioural tests. Overall, MRI is a very sensitive tool to obtain correlates for neuronal degeneration in vivo. Furthermore, MRI enables us to investigate a follow up at different time points of the disease. These advantages are especially useful for therapeutic studies with respect to survival rates of motor neurons using mouse models. Finally, our data suggest that MRI does not only resemble the findings of behavioural tests, but is potentially superior to behavioural studies.

Original languageEnglish (US)
Pages (from-to)1895-1901
Number of pages7
JournalEuropean Journal of Neuroscience
Volume26
Issue number7
DOIs
Publication statusPublished - Oct 2007
Externally publishedYes

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Keywords

  • Amyotrophic lateral sclerosis
  • Open-field behavioural test
  • Superoxide dismutase 1
  • T maps
  • Transverse relaxation time T

ASJC Scopus subject areas

  • Neuroscience(all)

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