Deafness, Tinnitus and Therapies

 Jean-Luc PUEL

 INM - U 1051

 80, rue Augustin Fliche, 34091 Montpellier

Phone: +33 4 99 63 60 05

Email: jean-luc.puel@inserm.fr

Website

Hearing impairment affects ~16% of the adult population and more than half of people over 60 years of age, making age-hearing loss a major health problem. In Europe, failure to address hearing impairments costs 213 billion Euros per year (22.4 billion Euros for 16% of French adults; Shield, Hear-it report, AISBL, 2006). Our goal is to unravel the mechanisms of deafness and tinnitus to envision therapies. This requires i) the analysis of animal mutants that recapitulate human auditory deficits, ii) to decipher the logic of sound coding, and iii) to develop new diagnostic tools for auditory disorders screening. To bolster translational research, we set-up special programs of interest through interplay between academic agencies, charity foundations and pharmaceutical or industrial companies.

Keywords: hearing, cochlea, sensory hair cell, auditory nerve

Main publications

• Menardo J, Tang Y, Ladrech S, Lenoir M, Casas F, Michel C, Bourien J, Ruel J, Rebillard G, Maurice T, Puel J-L, Wang J (2012) Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea. Antioxid Redox Signal 16:263–274.
• Fasquelle L, Scott HS, Lenoir M, Wang J, Rebillard G, Gaboyard S, Ventéo S, François F, Mausset-Bonnefont A-L, Antonarakis SE, Neidhart E, Chabbert C, Puel J-L, Guipponi M, Delprat B (2011) Tmprss3, a transmembrane serine protease deficient in human DFNB8/10 deafness, is critical for cochlear hair cell survival at the onset of hearing. J Biol Chem 286:17383–17397.
• Nouvian R, Neef J, Bulankina AV, Reisinger E, Pangršič T, Frank T, Sikorra S, Brose N, Binz T, Moser T (2011) Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins. Nat Neurosci 14:411–413.
• Ruel J, Chabbert C, Nouvian R, Bendris R, Eybalin M, Leger CL, Bourien J, Mersel M, Puel J-L (2008) Salicylate enables cochlear arachidonic-acid-sensitive NMDA receptor responses. J Neurosci 28:7313–7323.
• Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, van Rybroek JM, Rebillard G, Lenoir M, Eybalin M, Delprat B, Sivakumaran TA, Giros B, Mestikawy el S, Moser T, Smith RJH, Lesperance MM, Puel J-L (2008) Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet 83:278–292.
• Nouvian R (2007) Temperature enhances exocytosis efficiency at the mouse inner hair cell ribbon synapse. J Physiol (Lond) 584:535–542.
• Wang J, Ruel J, Ladrech S, Bonny C, van de Water TR, Puel J-L (2007) Inhibition of the c-Jun N-terminal kinase-mediated mitochondrial cell death pathway restores auditory function in sound-exposed animals. Mol Pharmacol 71:654–666.
• Venail F, Wang J, Ruel J, Ballana E, Rebillard G, Eybalin M, Arbones M, Bosch A, Puel JL (2007) Coxsackie adenovirus receptor and alpha nu beta3/alpha nu beta5 integrins in adenovirus gene transfer of rat cochlea. Gene Ther 14:30–37.
• Brugeaud A, Travo C, Demêmes D, Lenoir M, Llorens J, Puel J-L, Chabbert C (2007) Control of hair cell excitability by vestibular primary sensory neurons. J Neurosci 27:3503–3511.
• Khimich D, Nouvian R, Pujol R, Tom Dieck S, Egner A, Gundelfinger ED, Moser T (2005) Hair cell synaptic ribbons are essential for synchronous auditory signalling. Nature 434:889–894.