Project Details
Projekt
MR biomarkers of noise-induced hearing loss - studies of neurodegeneration, connectivity and neurotransmitter metabolism in the central auditory system of the mouse
Applicants
Professor Dr. Philipp Boehm-Sturm; Dr. Moritz Gröschel
Subject Area
Otolaryngology, Phoniatrics and Audiology
Clinical Neurology; Neurosurgery and Neuroradiology
Clinical Neurology; Neurosurgery and Neuroradiology
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 428869206
Partial or complete hearing loss is often accompanied by various psychoacoustic phenomena such as tinnitus, hyperacusis, impaired discrimination in noise, or a reduced speech comprehension. Therefore, detailed investigations of the underlying mechanisms leading to progressive hearing loss are of utmost importance. In recent years, it has become increasingly evident that noise trauma not only has an impact on peripheral cochlear structures but also causes prominent effects on the physiology and anatomy of auditory processing structures in the brain. The overarching goal of the proposed project is to develop and histologically validate noninvasive imaging biomarkers of neurodegenerative and neuroplastic processes using noise trauma-induced hearing loss as a model disease. Experimentally and clinically applicable prediction models for the derivation of neuropathological changes and corresponding functional measures based on Magnetic Resonance Imaging (MRI) will be developed. The project will be designed in a way that results can be transferred to other neurodegenerative processes, e.g. in cerebrovascular diseases or dementia. Noise-induced pathophysiological processes in the central auditory system of the mouse will be recorded at several consecutive times using non-invasive MRI. To this end, neurodegenerative processes will be investigated using voxel-based morphometric measurements (VBM), changes in structural connectivity will be mapped by diffusion tensor imaging (DTI) and modulation of synaptic plasticity in inhibitory and excitatory transmission will be analyzed by proton magnetic resonance spectroscopy (1H-MRS) in the auditory midbrain and thalamus. For each MR examination, tissue of these brain structures will be processed for immunohistochemical studies of neurodegeneration (cell and neuronal staining), axonal projections (staining of neurofilaments) and synaptic activity (representation of inhibitory and excitatory vesicular neurotransmitter transporter). Using linear models, the value of non-invasive MRI in terms of histological and functional outcome after noise trauma will be both qualitatively and quantitatively analyzed. The findings of the proposed project will serve as a basis for the development of novel MR-based diagnostic tools of noise-induced trauma in patients.
DFG Programme
Research Grants
