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Neuro inflammation

The group is investigating the molecular mechanisms of inflammation and differentiation of glial cells that are relevant during neurodegenerative and inflammatory events of the brain.

Using cell and molecular biology approaches, the objective of the team is to gain further insight into the pathophysiological events taking place during the onset and chronification of inflammatory reactions in the Central Nervous System (CNS) during neurodegenerative diseases like Alzheimer’s disease. The influence of typical neuroectodermal differentiation pathways (like the Notch pathway) as well as the effect of metabolic stress (via nuclear receptors) on this phenotype acquisition is analyzed. An important issue during lesion-induced chronic stress in the brain is the interplay between activated glial cells (astrocytes and microgliocytes) and the neural progenitor cells, which have the potential to repair the lesioned areas. The signaling events happening during the dialog between these cell types are studied. The implication of the Notch pathway in the activation of astrocytes and microglia is studied. A pharmacochemical approach is accompanying the basic research efforts in order to define molecular structures able to modulate the biological responses.

This translational research has allowed the group to participate in the creation of a start-up company in biotechnology called Axoglia.

Team members

Paul Heuschling started as Professor for Biology (cell and animal biology) in 2001 at the Centre Universitaire de Luxembourg, which became part of the Université du Luxembourg in 2003. Since late 2002, research activities started at the LNB. A collaborating scientist since 2001, Eleonora Morga joined the lab as assistant-professor in 2004. Since the start, the lab’s research interests have been focused on the phenotypic changes occurring during the differentiation process of normal glial cells towards gliosis. The team has extensive experience in handling primary cultures of neuronal and glial cells and is using techniques from cell and molecular biology, biochemistry and histology. Luc Grandbarbe joined the lab as a post-doc scientist in 2003 after having worked on the Notch-signalling pathway in neuronal stem cells and the glial differentiation at the Université Louis Pasteur in Strasbourg. Tony Heurtaux has joined the team in November 2005 after passing his PhD thesis on gliosis and oxidative stress at the Université Henri Poincaré in Nancy. Three PhD-students are currently working at the lab.

The neuro-inflammation team has a well-funded knowledge and competences in the biology of glial cells . It has proven expertise in the establishment of primary cell cultures, organotypic cultures and animal handling. At the operational level, the group of PH and EM has competences in cell biology, molecular biology, protein chemistry and immunocytochemistry applied to glial cells. PH is reviewer for several major international neuroscience journals ( Neurosci, J Neurochem, Glia, J Neuroimmunol, Brain Res, Brain Res Bul, etc.), and member of the European task force for brain research.

Publications since 2004

Peer-reviewed original publications

Morga E, Mouad-Amazzal L, Felten P, Heurtaux T, Moro M, Michelucci A, Gabel S, Grandbarbe L, Heuschling P (2009) Jagged1 regulates the activation of astrocytes via modulation of NFkappaB and JAK/STAT/SOCS pathways. Glia.

Michelucci A, Heurtaux T, Grandbarbe L, Morga E, Heuschling P (2009) Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: Effects of oligomeric and fibrillar amyloid-beta. J Neuroimmunol 210:3-12.

Grandbarbe L, Michelucci A, Heurtaux T, Hemmer K, Morga E, Heuschling P (2007) Notch signaling modulates the activation of microglial cells. Glia 55:1519-1530.

Hauss F, Liu J, Michelucci A, Coowar D, Morga E, Heuschling P, Luu B (2007) Dual bioactivity of resveratrol fatty alcohols: differentiation of neural stem cells and modulation of neuroinflammation. Bioorg Med Chem Lett 17:4218-4222.

Muller T, Grandbarbe L, Morga E, Heuschling P, Luu B (2004) Tocopherol long chain fatty alcohols decrease the production of TNF-alpha and NO radicals by activated microglial cells. Bioorg Med Chem Lett 14:6023-6026.

Patents

  1. Müller T, Heuschling P, Luu B, Composés promoteurs de la différenciation des précurseurs d’oligodendrocytes et modulateurs de l’activation microgliale, compositions et utilisations. FR03 11325, 2003
  2. Müller T., Morga E., Heuschling P., Luu B. Composés stimulateurs de la régénération et modulateurs des mécanismes inflammatoires du système nerveux central, compositions et utilisations. WO 2005/030748
  3. Hauss F., Michellucci A., Liu J., Grandbarbe L., Coowar D., Morga E., Heuschling P., Luu B. Composés neurotrophiques et neuroprotecteurs: hybrides resvératrol/alcool gras à longue chaîne. Demande nationale (FR) déposée en décembre 2005.