Laboratoire Neurodégénérescence et Régénération (LNR)

Laboratory Neurodegeneration and Regeneration

Principal Investigator : Charles Nicaise, PhD

charles.nicaise@unamur.be or 081/72.42.56

University of Namur, Faculty of Medicine, URPhyM – NARILIS, Building Medicine, 5th floor

Membres du LNR

PhD student : Joanna Bouchat, MSc

Alumni : Sarah Michel, Pharm D

 

Research and Clinical Interests

 

Overall Goals: Our laboratory has an interest in examining the in vivo role played by astrocytes and their glutamate transporters in the etiology of osmotic demyelination syndrome (ODS). ODS is part of non-inflammatory demyelinating diseases characterized by central pontine and/or extrapontine myelinolysis. The pathophysiology leading to demyelination and remyelination failure is not yet fully understood. Although being a demyelinating disease affecting myelin sheath integrity and oligodendrocytes viability, we recently demonstrated that, before any oligodendrocyte or myelin loss, astrocytes of the demyelinated areas unexpectedly died. Astrocytes are more and more recognized to fulfill important functions throughout the CNS. In particular, astrocytes support many neuronal functions, closely interact with oligodendrocytes and are responsible for the vast majority of CNS glutamate buffering through expression of glutamate transporters (GLT1 and GLAST). Despite their critical importance in the CNS, the roles played by astrocytes in neurological disorders such as neurodegeneration and demyelination have not been well elucidated.

 

Experimental Approaches: Employing a multidisciplinary approach that includes animal models of ODS, transgenic and knockout mouse models, stem cell transplantation (glial-restricted precursors cells or iPS-derived neural precursors), intraspinal viral vector-based manipulation of glutamate transporter levels, and extensive histological, biochemical, behavioral and in vivo physiological analyses, our goal is to both characterize the roles played by these astrocyte glutamate transporters in clinically-relevant functional outcomes following ODS.

 

Our ongoing projects aim to:

  1. Establish a new mouse model of ODS and confirm the involvement of astrocytes in myelin and oligodendrocyte loss.
  2. Examine the glutamate metabolism and the role of main astrocytic glutamate transporters (GLT1 and GLAST) during experimental ODS.
  3. Therapeutically target astrocyte replacement and astrocyte-specific functions (i.e. glutamate handling through GLT1) for the treatment of ODS via transplantation of glial precursors cells or iPS‐derived astrocytes.
  4. Unravel the contribution of astrocytes to glial scar following ODS: production of brain extracellular matrix proteins impairing axonal regrowth, remyelination and functional regeneration

 

List of publications:

http://directory.unamur.be/staff/nicaisec/publications