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Ultrastructural Analysis of Thalamus Damages in a Mouse Model of Osmotic-Induced Demyelination

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Abstract

A murine model used to investigate the osmotic demyelination syndrome (ODS) demonstrated ultrastructural damages in thalamus nuclei. Following chronic hyponatremia, significant myelinolysis was merely detected 48 h after the rapid reinstatement of normonatremia (ODS 48 h). In ODS samples, oligodendrocytes and astrocytes revealed injurious changes associated with a few cell deaths while both cell types seemed to endure a sort of survival strategy: (a) ODS 12 h oligodendrocytes displayed nucleoplasm with huge heterochromatic compaction, mitochondria hypertrophy, and most reclaimed an active NN cell aspect at ODS 48 h. (b) Astrocytes responded to the osmotic stress by overall cell shrinkage with clasmatodendrosis, these changes accompanied nucleus wrinkling, compacted and segregated nucleolus, destabilization of astrocyte-oligodendrocyte junctions, loss of typical GFAP filaments, and detection of round to oblong woolly, proteinaceous aggregates. ODS 48 h astrocytes regained an active nucleus aspect, without restituting GFAP filaments and still contained cytoplasmic proteinaceous deposits. (c) Sustaining minor shrinking defects at ODS 12 h, neurons showed slight axonal injury. At ODS 48 h, neuron cell bodies emerged again with deeply indented nucleus and, owing nucleolus translational activation, huge amounts of polysomes along with secretory-like activities. (d) In ODS, activated microglial cells got stuffed with huge lysosome bodies out of captures cell damages, leaving voids in interfascicular and sub-vascular neuropil. Following chronic hyponatremia, the murine thalamus restoration showed macroglial cells acutely turned off transcriptional and translational activities during ODS and progressively recovered activities, unless severely damaged cells underwent cell death, leading to neuropil disruption and demyelination.

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Abbreviations

ΔSNa+ :

Gradient of serum Na+

BBB:

Blood-brain barrier

CNS:

Central nervous system

GFAP:

Glial fibrillary acidic protein

HN:

Hyponatremic

NN:

Normonatremic

ODS:

Osmotic demyelination syndrome

RER:

Rough endoplasmic reticulum

SER:

Smooth endoplasmic reticulum

TEM:

Transmission electronic microscopy

VPL:

Ventral posterior lateral

VPM:

Ventral posterior medial

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Acknowledgments

We are grateful to C. Charlier and C. De Bona for their technical support. This research used the Electron Microscope facility of the “Plateforme Technologique Morphologie–Imagerie” of UNamur.

Funding

J.P.B was supported by grants from the Belgian “Fonds de la Recherche Scientifique Médicale” (T.0023.15) and the Belgian Foundation “Recherche Alzheimer/ Stichting Alzheimer Onderzoek” (14001) (Fund Aline).

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Author notes

  1. Joanna Bouchat and Jacques Gilloteaux contributed equally to this work.

Authors and Affiliations

  1. Unité de Recherche en Physiologie Moléculaire (URPhyM) – NARILIS, Faculté de Médecine, Université de Namur, Rue de Bruxelles 61, B-5000, Namur, Belgium

    Joanna Bouchat, Jacques Gilloteaux, Daniel Van Vlaender & Charles Nicaise

  2. Department of Anatomical Sciences, St George’s University School of Medicine, Newcastle upon Tyne, UK

    Jacques Gilloteaux

  3. Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, Brussels, Belgium

    Valérie Suain & Jean-Pierre Brion

Authors
  1. Joanna Bouchat
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  2. Jacques Gilloteaux
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  3. Valérie Suain
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  4. Daniel Van Vlaender
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  5. Jean-Pierre Brion
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  6. Charles Nicaise
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Corresponding author

Correspondence to Charles Nicaise.

Ethics declarations

The experimental protocol was conducted in compliance with the European Communities Council Directives for Animal Experiments (2010/63/EU, 87-848/EEC and 86/609/EEC) and was approved by the Animal Ethics Committee of University of Namur (Ethic project n°14-210).

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Supplemental Figure 1

Selection of samples for the condition 48 h post-correction. We selected right hemisphere for electron microscopy and used left hemisphere for contralateral control in histology. 0.69 mm punches were sampled thanks to myelin staining and anti-GFAP immunolabeling. Region 1 corresponds to the lesion in the posterior thalamic nuclear group. Region 2 is the perilesional gliotic area in zona incerta and region 3 corresponds to caudate putamen. Scale bar equals 1 mm for the staining and immunolabeling of contralateral hemisphere. (PNG 7533 kb)

High resolution image (TIF 10900 kb)

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Bouchat, J., Gilloteaux, J., Suain, V. et al. Ultrastructural Analysis of Thalamus Damages in a Mouse Model of Osmotic-Induced Demyelination. Neurotox Res 36, 144–162 (2019). https://doi.org/10.1007/s12640-019-00041-x

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  • DOI: https://doi.org/10.1007/s12640-019-00041-x

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