Institut des Neurosciences de Montpellier : Physiologie et physiopathologie de l’oreille interne

U583

Equipe 1
Génétique et thérapie des cécités rétiniennes

Equipe 2
Physiopathologie et thérapies de l’oreille interne

Equipe 3
Neurobiologie cellulaire et moléculaire du système somato-sensoriel

Equipe 4
Physiologie et approches thérapeutiques des pathologies médullaires

Equipe 5
Physiologie et thérapie des désordres vestibulaires

U844

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Jean-Luc Puel

Position : Professor of Neuroscience, University Montpellier 1

Academic and scientific Track :

Jean-Luc Puel started his scientific career in Montpellier in 1983 in the Inserm’s laboratory U254 (Laboratoire Neurobiologie de l'Audition) directed by Professor Rémy Pujol. In 1986, he defended his PhD thesis "frequency selectivity in rats during development and after ototoxic drugs administration" and joined Professor Richard P. Bobbin's laboratory (Department of Otorhinolaryngology, Louisiana State University, New-Orleans) as a post-doctoral fellow. During his postdoctoral training, he developed several research programs on the pharmacology of the cochlea. In 1989, he came back to France and was appointed as a researcher by the CNRS to develop pharmacological therapies of the inner ear. In 1998, Jean-Luc Puel became Director of Research at the CNRS. Later on, he obtained a position of Professor of Neuroscience at the University of Montpellier 1 and became director of the “Research centre for hearing aids” (CREFA) in 2001. During this period, he actively participated with Christian Hamel, Jean Valmier and Alain Privat to the creation of the Institute of Neurosciences of Montpellier (INM-Inserm U583). This institute, in which he manages the team of “Physiology and Therapy of the Inner Ear”, has been inaugurated in 2003.

Main achievements :

During his career, Jean-Luc Puel published 88 papers in international journal (h‑index : 27), 25 book chapters and more than 200 communications or posters. He is member of the Editorial Board for International Journals, scientific committees and societies. In addition to the fundamental researches, he took out 3 patents for potential tinnitus and deafness treatments and promoted clinical transfer of fundamental research.

Research interests :

Jean-Luc Puel's research interests are focused on the normal and pathological functioning of the inner ear. They include researches on the maintenance of cochlear fluid homeostasis, on the coding of the sensory message and on the promotion of post-traumatic regeneration of sensory epithelia. Interests are also clinically oriented researches on cochlear pathologies such as tinnitus and deafness.

Ion homeostasis and hereditary deafness : More than 50 % of the hereditary deafness comes from a defect of the homeostasis of the cochlear fluids. The Na,K-ATPase is a key protein in the endolymph homeostasis. We recently demonstrated that FXYD6 is an auxiliary protein able to control, in association with the Na,K-ATPase, the endolymph electrochemical equilibrium (Delprat et al., 2007). We are developping a knock out mice to study the function of FXYD6.

Integration of the sensory message and tinnitus : Glutamate is the neurotransmitter mediating fast synaptic transmission between the sensory hair cells and the auditory nerve fibers via AMPA-preferring receptors. This synapse is tonically regulated by dopamine (Ruel et al., 2006). We demonstrated in a behavioural animal model that tinnitus resulted from “abnormal” activation of NMDA receptors (Guitton et al, 2003). Targeting cochlear NMDA receptors may present a promising strategy to treat tinnitus.

Degeneration and protection of the cochlea : The auditory sensory cells are vulnerable to a variety of exogenous factors such as loud noise, aminoglycoside antibiotics and antimitotic drugs. We have previously shown that the mitochondrial pathway is extensively activated in cells in response to extracellular signals and internal insults (e.g. DNA damage). Based on these results, we designed therapeutic strategies using local applications of specific peptide inhibitors of JNK (Wang et al., 2007b), caspases (Wang et al., 2004) or calpains (Wang et al., 2007a).

Clinical transfer : A specialist tinnitus clinic has been created within the ENT department to better understand the mechanisms of tinnitus (Nicolas-Puel et al., 2006). We also study presbycusis in a 3-cities cohort (Montpellier, Bordeaux, and Dijon) to discriminate between genetic and environmental factors. In addition to human studies, we closely work with industrials (pharmacological companies, cochlear implant manufacturers) to test neuroprotective molecules (Venail et al., 2007).

10 selected publications :

Wang J., Pignol B., Chabrier PE., Lenoir M., Ruel J. and Puel J-L. A novel dual inhibitior of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma. Neuropharmacology 2007a, 52(6), 1426-37.

Wang J., Ruel J., Ladrech S., Bonny C., Van de Water TR. , Puel J-L. Inhibition of the JNK-mediated mitochondrial cell death pathway restores auditory function in sound exposed animals. Mol. Pharmacol. 2007b, 71 (3), 654-666.

Venail F., Wang J., Ruel J., Ballana E., Rebillard G., Eybalin M., Arbones M., Bosch A., Puel J.L. Coxsackie Adenovirus Receptor And αvβ3/αvβ5 Integrins In Adenovirus Gene Transfer In The Mammalian Cochlea. Gene Therapy 2007, 14(1):30-7.

Delprat B, Schaer D, Roy S, Wang J, Puel J-L, Geering K. FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear. J Biol Chem. 2007, 9;282(10), 7450-6.

J. Ruel, J. Wang, D. Demêmes, S. Gobaille, J-L Puel, G. Rebillard Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurons and their responsiveness to sound stimulation. J. of Neurochemistry2006; 97(1), 190-200.

Nicolas-Puel C., Lloyd R., Akbaraly T., Berr C., Uziel A., Rebillard G. and Puel J-L. Characteristics of tinnitus in a population of 555 patients: Specificities of tinnitus induced by noise trauma. International Tinnitus Journal2006, 12, 64-70.

Wang J., Ladrech S., Pujol R., Brabet Ph., Van De Water TR and Puel J.L. Caspase Inhibitors, but not c-Jun N-Terminal Kinase Inhibitor Treatment Prevents Cisplatin-Induced Hearing Loss. Cancer Research 2004, 64, 9217-9224.

Wang J, Van de vater T., Bonny C, Deribaupierre F, Puel J.L Zine A. Peptides inhibitor of c-Jun-N-terminal kinase (IB1/JIP‑1) protect against both aminoglycoside and acoustic trauma -Induced auditory hair cell death and hearing loss. J. Neurosci. 2003; 23, 8596-8607.

Guitton M.J., Caston J., Ruel J., Pujol R., Puel J-L. Salicylate induces tinnitus through activation of cochear NMDA receptors. J. Neurosci. 2003, 23, 3944-3952.

DELPRAT B., BOULANGER A.,WANG J., BEAUDOUIN V., GUITTON M.J., VENTEO S., DECHESNE C.J., PUJOL R., LAVIGNE-REBILLARD M., PUEL J.L., HAMEL C.P. Down regulation of Otospiralin, a novel Inner Ear Protein, causes hair cell degeneration and deafness. J. Neurosci. 2002, 22(5), 1718-1725.

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