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

Keywords

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

Publications

Rocher AB, Gubellini P, Merienne N, Boussicault L, Petit F, Gipchtein P, Jan C, Hantraye P, Brouillet E, Bonvento G.Synaptic scaling up in medium spiny neurons of aged BACHD mice: A slow-progression model of Huntington's disease.Neurobiol Dis. 2016 Feb;86:131-9. doi: 10.1016/j.nbd.2015.10.016. Epub 2015 Nov 25.

Boussicault L, Hérard 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, Véga C, Bonvento G. Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions. Glia. 2015 Jan;63(1):91-103. 

Merienne N, Le Douce J, Faivre E, Déglon N, Bonvento G. Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors. Front Neuroenergetics. 2013 May 31;5:5. 

Damiano M, Diguet E, Malgorn C, D?Aurelio M, Galvan L, Petit F, Benhaim L, Guillermier M, Houitte D, Dufour N, Hantraye P, Canals JM, Alberch J, Delzescaux T, Déglon N, Beal MF, Brouillet E (2013) Hum Mol Genetics, in press.

Galvan L, Lepejová N, Gaillard MC, Malgorn C, Guillermier M, Houitte D, Bonvento G, Petit F, Dufour N, Héry P, Gérard M, Elalouf JM, Déglon N, Brouillet E, de Chaldée M. (2012) Neurobiol Aging 33:1845.e5-6

Colin A, Faideau M, Dufour N, Auregan G, Hassig R, Andrieu T, Brouillet E, Hantraye P, Bonvento G, Déglon N (2009) Glia 57:667-79

Faideau M, Kim J, Cormier K, Gilmore R, Welch M, Auregan G, Dufour N, Guillermier M, Escartin C, Brouillet E, Hantraye P, Déglon, N, Ferrante RJ and Bonvento G Faideau M (2012) Human Mol Genet 19:3053-3067

Roux L, Benchenane K, Rothstein JD, Bonvento G, Giaume C. (2011) Proc Natl Acad Sci USA 108(45):18442-18446.
Martin C, Houitte D, Guillermier M, Petit F, Bonvento G, Gurden H. (2012) Front Neural Circuits 6:1

Escartin C, Rouach N. Front. Neuroenerg.. 2013. 5:4.
Lavisse, S, Guillermier, M, Herard, A S, Petit, F, Delahaye, M, Van Camp, N, Ben Haim, L, Lebon, V, Remy, P, Dolle, F, Delzescaux, T, Bonvento, G, Hantraye, P, and Escartin, C. (2012), J Neurosci 32, 10809-10818.

Marchadour, C., Brouillet, E., Hantraye, P., Lebon, V. and Valette, J. (2012) Anomalous diffusion of brain metabolites evidenced by diffusion-weighted magnetic resonance spectroscopy in vivo. J Cereb Blood Flow Metab, 32, 2153-60. Mochel, F., Durant, B., Meng, X., O'Callaghan, J., Yu, H., Brouillet, E., Wheeler, V.C., Humbert, S., Schiffmann, R. and Durr, A.

(2012) Early alterations of brain cellular energy homeostasis in Huntington disease models. The Journal of biological chemistry, 287, 1361-70.

Valette, J., Giraudeau, C., Marchadour, C., Djemai, B., Geffroy, F., Ghaly, M.A., Le Bihan, D., Hantraye, P., Lebon, V. and Lethimonnier, F. (2012) A new sequence for single-shot diffusion-weighted NMR spectroscopy by the trace of the diffusion tensor. Magnetic resonance in medicine 68, 1705-12.

Escartin, C., Won, S.J., Malgorn, C., Auregan, G., Berman, A.E., Chen, P.C., Deglon, N., Johnson, J.A., Suh, S.W. and Swanson, R.A. (2011) Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory amino acid transporter 3 expression. J Neurosci, 31, 7392-401.
Damiano, M., Galvan, L., Deglon, N. and Brouillet, E. (2010) Mitochondria in Huntington's disease. Biochim Biophys Acta, 1802, 52-61.

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.

Lab rotation

Deficit of synaptic plasticity in Alzheimer’s disease: role of astrocytes

Team leader: 

BONVENTO Gilles

Dates: 

January 2, 2018 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Learning and memory are crucial in the interaction of an individual with the environment and are fundamental brain processes that are affected in a large number of brain diseases including Alzheimer’s disease (AD). We hypothesize that, in addition to information processing by neurons, astrocytes play a fundamental role, yet under-estimated, in memory regulation and encoding. Our project aims to explore using cutting-edge methods (live calcium imaging in freely moving mice, WT and 3xTG) the contribution of astrocytes in memory formation by releasing gliotransmitters related to energy pathways.

Contact

MIRCen - 18 route du Panorama 92260 Fontenay-aux-Roses - +33 1 46 54 83 30 - gilles.bonvento@cea.fr

Supervisor: 

BONVENTO Gilles