Post-Mortem Analysis of Neuropathological Changes in Human Tinnitus

Abstract

Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients’ auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus.

Neural Plasticity in Tinnitus Mechanisms

“…Thus, it is important for tinnitus research to be grounded in studies of the postmortem brain from people who experienced tinnitus in life. The work by Almasabi et al [7] provided a rare example where it was possible to study tinnitus-related changes in the numbers of serotonergic and dopaminergic neurons, as well as evidence of neurodegeneration in brain structures that are associated with tinnitus. Reduced serotonin levels are particularly associated with depression, which is one of the main comorbidities linked to tinnitus distress, with the other being anxiety, which is particularly associated with structures such as the insular cortex [8].…”