Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson’s disease evaluated with multimodal MRI - Sorbonne Université Access content directly
Journal Articles PLoS ONE Year : 2018

Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson’s disease evaluated with multimodal MRI

Abstract

Parkinson's disease is characterized by neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta. The 6-hydroxydopamine (6-OHDA) rat model has been used to study neurodegeneration in the nigro-striatal dopaminergic system. The goal of this study was to evaluate the reliability of diffusion MRI and resting-state functional MRI biomarkers in monitoring neurodegeneration in the 6-OHDA rat model assessed by quantitative histology. We performed a unilateral injection of 6-OHDA in the striatum of Sprague Dawley rats to produce retrograde degeneration of the dopamine neurons in the substantia nigra pars compacta. We carried out a longitudinal study with a multi-modal approach combining structural and functional MRI together with quantitative histological validation to follow the effects of the lesion. Functional and structural connectivity were assessed in the brain of 6-OHDA rats and sham rats (NaCl injection) at 3 and 6 weeks post-lesioning using restingstate functional MRI and diffusion-weighted. Our results showed (i) increased functional connectivity in ipsi-and contra-lesioned regions of the cortico-basal ganglia network pathway including the motor cortex, the globus pallidus, and the striatum regions at 3 weeks; (ii) increased fractional anisotropy (FA) in the ipsi-and contralateral striatum of the 6-OHDA group at 3 weeks, and increased axial diffusivity (AD) and mean diffusivity in the ipsilateral striatum at 6 weeks; (iii) a trend for increased FA in both substantia nigra of the 6-OHDA group at 3 weeks. Optical density measurements of tyrosine-hydroxylase (TH) staining of the striatum showed good correlations with the FA and AD measurements in the striatum. No correlations were found between the number of TH-stained dopaminergic neurons and MRI measurements in the substantia nigra. This study suggested that (i) FA and AD were reliable biomarkers to evaluate neurodegeneration in the cortico-basal ganglia network of the 6-OHDA model, (ii) diffusion MRI and resting-state functional MRI (rsfMRI) were not sensitive enough to detect changes in the substantia nigra in this model.
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hal-04404899 , version 1 (19-01-2024)

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Vincent Perlbarg, Justine Lambert, Benjamin Butler, Mehdi Felfli, Romain Valabrègue, et al.. Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson’s disease evaluated with multimodal MRI. PLoS ONE, 2018, 13 (9), pp.e0202597. ⟨10.1371/journal.pone.0202597⟩. ⟨hal-04404899⟩
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