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Translational Auditory Neuroscience

The goal of the laboratory is to increase the understanding of the mechanisms underlying hearing loss and the maladaptive plasticity occurring during tinnitus with hopes to develop new treatments and drugs to improve hearing function and silence tinnitus.

Hearing deficits are expected to affect 900 million individuals world- wide in 2025, and has recently ranked 4th in the leading causes of years lived with disability (WHO).

One of the most prevalent and distressing condition associated with hearing loss is tinnitus, or ringing in the ears, which is defined by the perception of sounds in spite of their physical absence. This neurological disorder affects 10-15% of the population and is predicted to double in Europe by 2050. In 1 out of ten, severe tinnitus distracts sufferers from work, interferes with concentration and sleep, increases the risk of disability pension and can be so severe as to trigger suicide. Both patients and therapists are highly unsatisfied by the available therapeutic options, and ENTs most often recommend patients to “live with it”. This is in part due to the lack of fundamental knowledge on the mechanisms causing tinnitus, and those making it persistent and severe.

Our research

The goal of the laboratory is to increase the understanding of the mechanisms underlying hearing loss and the maladaptive plasticity occurring during tinnitus with hopes to develop new treatments and drugs to improve hearing function and silence tinnitus.

For this purpose, we have established collaborations with both clinical researchers and the industry to facilitate the translation of our findings into cures.

The laboratory focuses on:

  • i) the molecular mechanisms that regulate synaptic uncoupling in the ear
  • ii) the mechanisms that govern homeostatic plasticity in the brain during tinnitus
  • iii) the causative relationship between peripheral damage and phantom sound generation.

We have a dual approach using animal models of hearing loss and tinnitus to decipher the signaling pathways disrupted in the ear and/or in the brain but also using genetics in multi-case families with history of tinnitus, having in aim the identification and validation of new targets for drug development.

To address this challenge, we use a battery of techniques including behavior, neuroimaging, auditory electrophysiology, molecular biology, synaptic histology, cell culture, cytometry, mouse and human genetics and epidemiology.

Group members

Christopher Cederroth - Associate Professor, group leader

Evangelia Tserga - PhD student

Natalia Trpchevska - PhD student

Niklas Edvall - Audiologist, Associated

Former group members

Rocio Paublete - Postdoc (2015-2017)

Kim Vikhe Patil - Master student (2016)

Rotation and internships

Eleni Genistarditi (2018) – visiting PhD student

Edis Gunan (2018) – Summer Research School student

Matilda Prada Hellberg (2018) - Summer Research School student

Lucy Yeung (2015) – visiting student

Xi Liu (2014) – trainee

Projects

Tinnitus development: role of glutamate transporters

Using mouse genetics, we identified a role for glutamate transporters in regulating tinnitus. We are now characterizing the mechanisms by which disruption in glutamate homeostasis causes a phantom sound percept.

The main aim is to characterize the functional and molecular consequences of glutamate-mediated de-afferentation in the cochlea. Our working hypothesis is that excess glutamate release in the cochlea causes overexcitation of the auditory neurons, hyperactivate auditory relays, reorganize the auditory cortex and subsequent tinnitus.

The ultimate goal is to provide a better understanding of the ear to brain interactions. These results may have a broad clinical application, contributing to the detailed understanding of normal auditory physiology, as well as the origins of tinnitus resulting from subtle auditory dysfunctions.

STOP: Swedish Tinnitus Outreach Project

Tinnitus is a very heterogeneous disorder. Distinct forms of tinnitus cannot respond as well to the same therapeutic intervention.

The goals of this study are to identify determinants of tinnitus, and use a comprehensive approach to classify tinnitus patients according to subtypes by means of questionnaires and auditory assessment in order to evaluate the prevalence of each form of tinnitus.

In a second step, we want to identify homogeneous sub-groups and perform genetic analyses to define new endophenotypes for a more accurate diagnostic of tinnitus patients at the clinic.

See the Swedish Tinnitus Outreach Project (STOP) for more information.

COMiT: Establishment of international Core Outcome Measures In Tinnitus

Within the TINNET consortium, we are working to identify and prioritize core domain sets for tinnitus. A core domain set for tinnitus would be the basic building block for developing a world-wide standardization on outcome measures.

TODD: Tinnitus Objective Diagnostic Device

An important gap in the care of tinnitus patients is the lack of robust objective methodologies to diagnose tinnitus.

This project aims to translate to humans an objective measure of tinnitus developed in animals.

Research support

  • H2020 ITN (ESIT)
  • Department of Defense
  • National Institute on Deafness and Other Communication Disorders (NIDCD), from the National Institute of Health (NIH)
  • Vetenskapsrådet
  • Svenska Läkaresällskapet
  • Lars Hiertas Minne
  • Magnus Bergvalls Stiftelse
  • Loo och Hans Ostermans
  • Tysta Skolan
  • Hörselforskningsfonden
  • Karolinska Institutet

Collaborations

National collaborators

International collaborators

  • Professor Berthold Langguth, University Hospital of Regensburg, Germany
  • Professor Deborah Hall, University of Nottingham, UK
  • Professor Birgit Mazurek, Chartié Hospital, Germany
  • Dr. Silvano Gallus, Institute of Research Mario Negri, Italy
  • Professor Jan Bulla, University of Bergen, Norway

Articles/Publications

Circadian Regulation of Cochlear Sensitivity to Noise by Circulating Glucocorticoids
Cederroth C, Park J-S, Basinou V, Weger B, Tserga E, Sarlus H, Magnusson A, Kadri N, Gachon F, Canlon B
Current Biology, 25 July 2019, DOI: https://doi.org/10.1016/j.cub.2019.06.057

Therapeutic Approaches to the Treatment of Tinnitus.
Langguth B, Elgoyhen AB, Cederroth CR
Annu. Rev. Pharmacol. Toxicol. 2019 Jan;59():291-313

Differential Phase Arrangement of Cellular Clocks along the Tonotopic Axis of the Mouse Cochlea Ex Vivo.
Park JS, Cederroth CR, Basinou V, Sweetapple L, Buijink R, Lundkvist GB, et al
Curr. Biol. 2017 Sep;27(17):2623-2629.e2

Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort.
Maas IL, Brüggemann P, Requena T, Bulla J, Edvall NK, Hjelmborg JVB, et al
Genet. Med. 2017 09;19(9):1007-1012

TrkB-mediated protection against circadian sensitivity to noise trauma in the murine cochlea.
Meltser I, Cederroth CR, Basinou V, Savelyev S, Lundkvist GS, Canlon B
Curr. Biol. 2014 Mar;24(6):658-63

Hearing loss and tinnitus--are funders and industry listening?
Cederroth CR, Canlon B, Langguth B
Nat. Biotechnol. 2013 Nov;31(11):972-4

Dissertations

2017 - Vasiliki Basinou, PhD
Title of thesis: Circadian rhythms in the auditory system
Department of Physiology and Pharmacology, Karolinska Institutet

2009 - Christopher R. Cedderroth, PhD
Title of thesis: Endocrine Disruptors and the Fetal Origin of Diseases.
Department of Genetic Medicine and Development, University of Geneva, Switzerland.

Contact

Christopher Cederroth

Research team leader
Translational Audiotory Neuroscience
Department of Physiology and Pharmacology (FYFA), C3