Activation of JNK in the Inner Ear following Impulse Noise Exposure

Abstract

Noise exposure is known to induce cell death signaling in the cochlea. Since c-Jun N-terminal kinase (JNK) signaling is known to induce both cell survival and apoptosis, the present study focused on early changes (within 24 h) after impulse noise exposure, inquiring whether cell death is always related to phosphorylation of JNK in the inner ear. Anesthetized adult albino rats were exposed to a single impulse noise exposure (194 kPa) and sacrificed 3 or 24 h later. Paraffin-embedded sections were examined for positive staining of phosphorylated JNK and the presence of cells with fragmented DNA (TUNEL staining). Positive TUNEL staining was observed at the spiral limbus and in the stria vascularis at 24 h following impulse noise exposure, but no correlation with JNK activation was found at these locations. In the hearing organ (organ of Corti) and in the lateral wall, TUNEL-reactive cells were observed at 24 h following trauma. This was preceded by p-JNK staining at 3 h, indicating JNK-activated cell death in these regions. Finally, p-JNK reactivity was observed in the spiral ganglion with no correlation to TUNEL staining within the time frame of this study. These results suggest that JNK activation following impulse noise exposure may not always be related to cell death, and conversely, some cells may die through JNK-independent signaling.

Mechanisms of blast induced brain injuries, experimental studies in rats

“…No structural damage was observed in the brain, although we have observed cell death in the cochlea in the same exposed animals and published gene array data on the regulation of apoptosis genes in this end-organ (Kirkegaard et al, 2006;Murai et al, 2008). A previous study using MRI (4.7 Tesla) after the exposure to a similar blast did not indicate any significant changes in brain T2 or ADC maps.…”

“…A level of 196 kPa was used for the gene array experiments. This pressure level has been used in previous studies on cell death in the inner ear (Kirkegaard et al, 2006;Murai et al, 2008) and MRI as well as EEG analysis (Risling et al, 2002a,b). Three exposed and three sham exposed animals (anesthetized and mounted in the tube) were used for the gene array studies.…”

Protecting the auditory system with glucocorticoids

“…These cellular cascades include mitogen activated protein kinases (MAPKs) (Meltser et al, 2009a;Murai et al, 2008;Selivanova et al, 2007;Wang et al, 2007) and a corticosteroid dependent transcription factor that has recently been found to mediate cochlear protection against acoustic trauma (Peppi et al, 2011). This transcription factor, PLZF, a promyelocytic leukemia zinc finger protein, is located in similar tissues of the inner ear that contain GR and mice deficient in PLZF do not demonstrate corticosteroid-related protection against acoustic trauma after sound conditioning or RS.…”

Molecular aspects of tinnitus

“…After acoustic trauma (continuous exposure or impulse noise), c-Jun N-terminal kinase (JNK), one of the mitogen-activated protein kinases (MAPKs) pathway, is activated in outer hair cells through intracellular Ca 2+ activation leading to outer hair cell death (Zine and van de Water, 2004;Murai et al, 2008;Meltser et al, 2009). Accordingly, AM-111, a cell-permeable peptide that selectively blocks JNK/MAPK-mediated apoptosis of stress-injured hair cells and neurons in the cochlea, protects from noise-induced hearing loss (Pirvola et al, 2000;Wang et al, 2003;Matsui et al, 2004;Zine and van de Water, 2004;Kirkegaard et al, 2006;Barkdull et al, 2007;Eshraghi et al, 2007;Shim et al, 2009), see Fig.…”