Heavy Metal-Induced Hair Cell Death

I have recently expanded my research interests to look at hair cell death in response to environmental toxins, such as heavy metals. Our lab has found that the heavy metal cadmium can reliably kill hair cells of the zebrafish lateral line as shown below (Schmid et al., 2020).

Similar to aminoglycoside-induced hair cell death mechanotransduction activity seems to be important for cadmium-induced hair cell death. Also while cilia genes with altered mechanotransduction activity are resistant to cadmium-induced hair cell death, similar to aminoglycosides, transition zone mutants with normal hair cell mechanotransduction activity show now resistance to cadmium-induced hair cell death. This suggests heavy metals and aminoglycosides might have different intracellular mechanisms once inside the hair cells resulting in cell death. This point is further supported by the fact that inhibiting calcium transfer in hair cells does not protect against cadmium-induced hair cell death the way it does against aminoglycoside-induced hair cell death (Galdieri et al., 2023).

Additionally, we have found cadmium treatment increases pAkt levels in hair cells and pERK levels in supporting cells. This is shown below in images of neuromasts from fish treated with cadmium where hair cells are labelled in green and pAkt or pERK in magenta as indicated. We believe the activation of these pathways may partially protect hair cells as inhibiting them leads to increased hair cell death (Galdieri et al., 2023).

A series of images of clusters of cells. On the left are clusters of green hair cells. In the middle are labels showing either pAkt which overlaps with the green hair cells or pERK which does not overlap with the hair cells. On the right are merged images.

In the future we risk to further investigate the molecular mechanisms of cadmium-induced hair cell death as well as investigating how other heavy metals impact hair cells.