Recent data have suggested that the dysfunction or selective death of neuronal populations, which are at risk in all neurodegenerative diseases, is not exclusively due to deleterious mechanisms limited to neurons. There are several lines of evidence to suggest that the neurodegeneration observed in
Huntington’s disease (HD) and
Alzheimer’s disease (AD) is influenced by a
dysfunction of glial cells,
astrocytes in particular.
Our research activities focus on the
interactions between neurons and astrocytes, particularly as concerns the regulation of energy metabolism. Indeed, it has been shown that astrocytes play a key role in ensuring the supply of energy to synapses, which have a high energy requirement and are very vulnerable during the stress states that may occur during neurodegenerative diseases. A disturbance of the metabolic interactions between astrocytes and neurons could therefore jeopardize the function and survival of neurons. Our research projects aim to determine the cellular origin of the disturbances of energy metabolism observed in AD. We use transgenic mouse models of AD (3xTg) recapitulating the metabolic deficits observed in patients. We also use cell culture, FRET cell imaging, 3D metabolic imaging in vivo and electrophysiological recordings on tissue slices to elucidate the mechanisms regulating the production and subcellular use of energy.
Development of viral vectors (AAVs) targeting astrocytes in the hippocampus and striatum
Team members - Marianne Maugard (doctorante): thèse de Neurosciences, Paris Saclay
- Pierre-Antoine Vigneron (doctorant) : thèse de Neurosciences, Paris Saclay
- Claire Séris (Master 2, UPMC)
Previous team members- Carole Escartin PhD, UPMC
- Angélique Colin PhD, UPMC
- Mathilde Faideau PhD, UPMC
- Lydie Boussicault PhD, UPMC
- Juliette Le Douce PhD, UPMC
- Claire Martin (post-doctorante)
- Anne Rocher (post-doctorante)
- Emilie Faivre (post-doctorante)
- Pierrick Jego (post-doctorant) Eurotalents EU
- Association France Alzheimer / Fondation de France (janvier 2013 – janvier 2016) : Bruno Cauli (CNRS UMR 7102, UMPC), Stéphane Oliet (INSERM U862, Bordeaux) Towards a gene therapy targeting astrocytes in AD
- Fondation Plan Alzheimer (Janvier 2016-janvier 2018) Role of astrocytic 3-phosphoglycerate dehydrogenase in AD
Recent publications
Current technical approaches to brain energy metabolism
Barros LF, Bolaños JP, Bonvento G, Bouzier-Sore AK, Brown A, Hirrlinger J, Kasparov S, Kirchhoff F, Murphy AN, Pellerin L, Robinson MB, Weber B.
Glia. 2017 Nov 7. Imaging and spectroscopic approaches to probe brain energy metabolism dysregulation in neurodegenerative diseases
Bonvento G, Valette J, Flament J, Mochel F, Brouillet E.
J Cereb Blood Flow Metab. 2017 Jun;37(6):1927-1943. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes
Lopez-Fabuel I, Le Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A, Bolaños JP.
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13063-13068 Synaptic scaling up in medium spiny neurons of aged BACHD mice: A slow-progression model of Huntington's disease
Rocher AB, Gubellini P, Merienne N, Boussicault L, Petit F, Gipchtein P, Jan C, Hantraye P, Brouillet E, Bonvento G.
Neurobiol Dis. 2016 Feb;86:131-139 Plasticity of astroglial networks in olfactory glomeruli
Roux L, Benchenane K, Rothstein JD, Bonvento G, Giaume C. (2011)
Proc Natl Acad Sci USA 108(45):18442-18446.
In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's Disease subjects
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 (2010)
Hum Mol Genetics, 19:3053-3067 Plasticity of astroglial networks in olfactory glomeruli
Roux L, Benchenane K, Rothstein JD, Bonvento G, Giaume C. (2011)
Proc Natl Acad Sci USA 108(45):18442-18446.
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