Loss of Ephaptic Contacts in the Murine Thalamus during Osmotic Demyelination Syndrome

ABSTRACT

Background and aim

A murine model mimicking osmotic demyelination syndrome (ODS) revealed with histology in the relay posterolateral (VPL) and ventral posteromedial (VPM) thalamic nuclei adjoined nerve cell bodies in chronic hyponatremia, amongst the damaged 12 h and 48 h after reinstatement of osmolality. This report aims to verify and complement with ultrastructure other neurophysiology, immunohistochemistry, and molecular biochemistry data to assess the connexin-36 protein, as part of those hinted close contacts.

This ODS investigation included four groups of mice: Sham (NN; n = 13), hyponatremic (HN; n = 11), those sacrificed 12 h after a fast restoration of normal natremia (ODS12h; n = 6) and mice sacrificed 48 h afterward, or ODS48 h (n = 9). Out of these, thalamic zones samples included NN (n = 2), HN (n = 2), ODS12h (n = 3) and ODS48h (n = 3).

Results

Ultrastructure illustrated junctions between nerve cell bodies that were immunolabeled with connexin36 (Cx36) with light microscopy and Western blots. These cell’s junctions were reminiscent of low resistance junctions characterized in other regions of the CNS with electrophysiology. Contiguous neurons showed neurolemma contacts in intact and damaged tissues according to their location in the ODS zones, at 12 h and 48 h post correction along with other demyelinating alterations. Neurons and ephaptic contact measurements indicated the highest alterations, including nerve cell necrosis in the ODS epicenter and damages decreased toward the outskirts of the demyelinated zone.

Conclusion

Ephapses contained C × 36between intact or ODS injured neurons in the thalamus appeared to be resilient beyond the core degraded tissue injuries. These could maintain intercellular ionic and metabolite exchanges between these lesser injured regions and, thus, would partake to some brain plasticity repairs.

KEYWORDS:

• Ephapsis
• Mouse
• Neurons
• ODS
• Thalamus

Acknowledgments

JP B was supported by grants T.0023.15 from the Belgian grant: “Fonds de la Recherche Scientifique Médicale” and the Belgian Foundation “Recherche Alzheimer/Stichting Alzheimer Onderzoek” (14001; Fund Aline). This study was performed in the Electron Microscope facility of the” Plateforme Technologique Morphologie - Imagerie” of the Université de Namur with the technical assistance of Corry Charlier. We thank Joanna Bouchat for having safely stored and made available all the biological samples.

Disclosure statement

The authors declare that the research has been conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

The work was supported by the none “Fonds de la Recherche Scientifique Médicale” , Brussels, Belgium [Grant T.0023.15]; the Belgian Foundation “Recherche Alzheimer/Stichting Alzheimer Onderzoek” (14001; Fund Aline). [14001].