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Purinergic mediated neuroinflammation and brain disorders

IMN

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Neurological disorders rely on alterations of the central or peripheral nervous system that are caused by impairments of neuronal transmission or more global perturbations of local circuits that implicate glial cells. The scientific goal of our team is to understand the contribution of neuronal versus inflammatory signaling in brain disorders including amyotrophic lateral sclerosis (ALS), attention deficit/hyperactivity disorders (ADHD), chronic pain, and anxiety-related disorders. Our objectives are to determine (i) the contribution of purinergic signaling as a dual system, and (ii) the modulatory function of peptidergic signaling, both capable to regulate neuronal synaptic activation and microglial neuro-inflammatory reaction as well as developmental processes. We combine cellular, anatomical, functional and behavioral approaches from in vitro to animal models. We expect to reveal the respective contribution of neuronal versus inflammation signaling in several central disorders and to provide attractive novel strategies and cellular targets to cure these disorders.

Selected publications

Bertin E, Deluc T, Pilch KS, Martinez A, Pougnet JT, Doudnikoff E, Allain AE, Bergmann P, Russeau M, Toulmé E, Bezard E, Koch-Nolte F, Séguéla P, Lévi S, Bontempi B, Georges F, Bertrand S, Nicole O and Boué-Grabot E.
Increased surface P2X4 receptor regulates anxiety and memory in P2X4 internalization-defective knock-in mice. Molecular Psychiatry, 2020, DOI : 10. 1038/s41380-019-0641-8

Papon MA, Le Feuvre Y, Barreda-Gomez G, Favereaux A, Farrugia F, Bouali-Benazzouz R, Nagy F, Rodriguez-Puertas R, Landry M (2020)
Spinal inhibition of GABAB receptors by the extracellular matrix protein fibulin-2 in neuropathic rats. Frontiers in Cell. Neurosci. 14:214. doi: 10.3389/fncel.2020.00214.

Duveau A, Bertin E and Boué-Grabot E (2020)
Implication of neuronal versus microglial P2X4 receptors in central nervous system disorders. Neurosci. Bull. published online ahead of print, 2020 Sep 5]. Neurosci Bull. 2020;10.1007/s12264-020-00570-y. doi:10.1007/s12264-020-00570-y

Roca-Lapirot O, Fossat P, Ma S, Egron K, Trigilio G, López-González MJ, Covita J, Bouali-Benazzouz R, Favereaux A, Gundlach AL and Landry M.
Acquisition of analgesic properties by the cholecystokinin/CCK2 receptor system within the amygdala in a persistent inflammatory pain condition. Pain, 2019, 160(2): 345-357.

Blanchard C, Boué-Grabot E and Massé K.
Comparative embryonic spatio-temporal expression profile map of the Xenopus P2X receptor family. Frontiers in Cellular Neuroscience, 2019, 13: 340. doi: 10. 3389/fncel. 2019. 00340

Magiera M, Bodakuntla S, Žiak J, Lacomme S, Marques Sousa P, Leboucher S, Hausrat TJ, Bosc C, Andrieux A, Kneussel M, Landry M, Calas A, Balastik M and Janke C. Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. EMBO J, 2018, 37(23). pii: e100440.

Bouchatta O, Manouze H, Bouali-Benazzouz R, Kerekes N, Ba M’Hamed S, Fossat P, Landry M* and Bennis M*.
Neonatal 6-OHDA lesion model in mouse induces Attention-Deficit/ Hyperactivity Disorder (ADHD)-like behaviour. Scientific Report, 2018, 8(1): 15349 (*co-senior authors).

Zaky A, Bouali-Benazzouz R, Favereaux A, Tell G, Landry M. (2018)
APE1/Ref-1 redox function contributes to inflammatory pain sensitization.
Exp. Neurol. 307:1-11

López-González MJ, Landry M and Favereaux A.
MicroRNA and chronic pain: From mechanisms to therapeutic potential.
Pharmacol Ther, 2017,  S0163-7258(17)30144-4

Boué-Grabot E and Pankratov Y (2017)
Modulation of central synapses by astrocyte-released ATP and postsynaptic P2X receptors.
Neural Plasticity 2017:9454275. doi: 10.1155/2017/9454275. PMID: 28845311

Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C and Koch-Nolte F.
Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation
Science Translational Medicine, 2016, 8, Issue 366, pp. 366ra162 DOI: 10. 1126/scitranslmed. aaf8463. PMID: 27881823

Radwani H, Lopez-Gonzalez M, Dobremez E, Eriksdottir E, Langel Ü, Favereaux A, Landry M* , Fossat P*.
Differential effect of L-type calcium channel subunits in pain transmission and pain sensitization. (2016)
J. Physiology (London), 594(22):6607-6626. (*co-senior authors).

Pougnet J-T, Compans B, Martinez A, Choquet D, Hosy E, and Boué-Grabot E. (2016)
P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CamKII phosphorylation sites on GluA1 in hippocampal neurons
Scientific Reports, 6, 31836. doi: 10.1038/srep31836.

Emerit M, Baranowski C, Diaz J, Martinez A, Areias J, Alterio J Masson J, Boué-Grabot E, and Darmon M (2016)
A new mechanism of receptor targeting by interaction between two classes of ligand-gated ion channels.
J. Neurosci. 36(5)1456-1470. PMID: 26843630

Engeln M, Bastide M, Toulme E, Dehay B, , Bourdenx M, Doudnikoff E, Li Q, Gross C, Boué-Grabot E, Pisani A , Bezard E and Fernagut PO. Selective inactivation of striatal FosB-expressing neurons alleviates L-Dopa-induced dyskinesia.
Biol Psychiatry, 2016 Mar 1; 79(5): 354-61. doi: 10. 1016/j. biopsych. 2014. 07. 007. PMID: 25146322

Romanov R. , Alpar A. , Zhang M. D. , Zeisel A. , Calas A. , Landry M. , Schnell R. , Dobolyi A. , Olah M. , Spence L. , Mulder J. , Martens P. , Palkovits M. , Uhlen M. , Sitte H. H. , Wagner L. , Linnarson S. , Hökfelt T. and Harkany T. (2015)
A secretagogin locus of the mammalian hypothalamus controls stress hormone release.
EMBO J. 34(1): 36-54.

Pougnet J-T, Toulmé E, Martinez A, Choquet D, Hosy E, and Boué-Grabot E. (2014)
ATP P2X receptors down-regulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons.
Neuron 83(2):417-430. doi: 10.1016/j.neuron.2014.06.005. PMID: 25033184

Team leader

Team member(s)


Eric Boué-Grabot (Researcher)
Marc Landry (Team leader - BIC Deputy platform leader)


Chercheurs, Praticiens hospitaliers...

André Calas (University teacher-researcher)
Karine Massé (University Teacher- Researcher)


Ingénieur(e)s, technicien(ne)s

Audrey Martinez
Louison Brochoire


Post-doctorant(s)


Doctorant(s)

Cynthia Khoury Abboud
Alexia Duveau