I'm assuming people are aware that these are links to press releases, and press releases should be treated like any other advertising.
Has anyone actually read the paper? I've posted the title and abstract below as well as a link to the paper which I believe is freely available. It's worth noting up front that this isn't a paper about testing drugs or some type of genetic modification to treat tinnitus. Moreover, they induced tinnitus via salicylate administration (i.e. aspirin) so it isn't clear how the conclusions would apply more generally though they do discuss noise induced tinnitus.
At a minimum it seems like the results should improve the measurement of tinnitus in mice - assuming the acoustic startle response measurements are doing what the people using them think they are doing. There is some debate for the effectiveness of ASR in measuring tinnitus (
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411996/).
The possibility that varying levels of GLAST are related to vulnerability to tinnitus or other hearing issues is quite interesting. It would be very useful to be able to screen for such vulnerability, and I hope someone follows up on their suggestion for genetic analysis of people with and without tinnitus (or potentially other hearing issues). It wouldn't prove a causal relationship, but it may provide another piece of the puzzle. Hopefully some of the places that do genetic testing for hearing issues will include EAAT1 in their tests. MORL at U of Iowa does not presently (
http://www.medicine.uiowa.edu/morl/otoscopegenes/) test EAAT1.
Finally, the relationship of GLAST to anxiety and schizophrenia is noteworthy. They raise the possibility that low levels of GLAST result in increased baseline anxiety and that this may exacerbate tinnitus intensity if not cause the tinnitus.
Regarding a few of the comments...
If the authors are correct, reducing or eliminating the expression of this gene will increase vulnerability to tinnitus. What would be required would be to increase its expression.
There is no mention in the text of channel blockers though a couple of papers are referenced. This isn't a paper about testing drugs.
Title:
GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus
Abstract:
Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.
Paper: http://journal.frontiersin.org/arti...campaign=ECO_FNBEH_20160901_cederrothtinnitus
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