Cell-cell interactions in neurodegenerative diseases

Leader

Research center

18 route du Panorama
92260 Fontenay-aux-Roses
Philippe Hantraye

Institution

CEA
CNRS
ED568 Biosigne
Université Paris Sud 11

Laboratory

Laboratoire des Maladies Neurodégénératives
UMR 9199
NEURATRIS

Mots clefs

neuron-astrocyte interactions
Mechanisms underlying region specificity in neurodegeneration
Role of reactive astrocytes
Available to host a PhD student

publications

 Bonvento G, Valette J, Flament J, Mochel F, Brouillet E. (2017) Imaging and spectroscopic approaches to probe brain energy metabolism dysregulation in neurodegenerative diseases. J Cereb Blood Flow Metab. 37:1927-1943

 

Lopez-Fabuel I, Le Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A, Bolaños JP. (2016) Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc Natl Acad Sci USA 113:13063-13068

Palombo M, Ligneul C, Najac C, Le Douce J, Flament J, Escartin C, Hantraye P, Brouillet E, Bonvento G, Valette J (2016) New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo. Proc Natl Acad Sci U S A 113:6671-6676

Ben Haim L, Ceyzeriat K, Carrillo-de Sauvage MA, Aubry F, Auregan G, Guillermier M, Ruiz M, Petit F, Houitte D, Faivre E, Vandesquille M, Aron-Badin R, Dhenain M, Deglon N, Hantraye P, Brouillet E, Bonvento G, Escartin C (2015) The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases. J Neurosci 35:2817-2829.

Boussicault L, Herard AS, Calingasan N, Petit F, Malgorn C, Merienne N, Jan C, Gaillard MC, Lerchundi R, Barros LF, Escartin C, Delzescaux T, Mariani J, Hantraye P, Beal MF, Brouillet E, Vega C, Bonvento G (2014) Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions. J Cereb Blood Flow Metab 34:1500-1510.

Fields of research

Neurological and psychiatric diseases

Research Theme

Our research focuses on the interactions between neurons and astrocytes, at the fundamental level but also in the context of neurodegenerative diseases in which glial cells display an activated phenotype that is not yet characterized at the functional level. These glial cells play an important role in brain function, particularly in energy metabolism, a function impaired in most neurodegenerative diseases (Alzheimer, Huntington and Parkinson). Our recent work shows that astrocytes activated by a cytokine (CNTF) effectively protect neurons from energy deficits (Escartin et al., 2006, 2007). One main objective is to develop new therapeutic approaches that target astrocytes and not only neurons, in particular through the use of new viral vectors (Colin et al., 2009). A pre-clinical trial of gene therapy in primates and of clinical phase I in humans is underway with a lentivirus encoding the CNTF. Our current projects seek to determine (1) the functional consequences of astrocyte activation (2) the role of astrocytes in the pathogenesis of Huntington's disease, (3) the factors that contribute to the vulnerability of striatal neurons in Huntington's disease and (4) the metabolic status of selectively affected cells in Alzheimer disease. Experimental approaches include the use of viral vectors in vivo and in vitro and measurements of functional indexes using molecular, biochemical, anatomical, electrophysiological and imaging tools.