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. 2019 Dec 8;11(23):11541–11564. doi: 10.18632/aging.102553

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Copyright © 2019 Lee et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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K_Na1 DKO mice have reduced and delayed wave I auditory brainstem responses (ABR) but normal absolute thresholds from ages 1 to 3-mo-old in comparison with WT animals, and by 6-mo-old, showed a profound increase in absolute thresholds, relative to the WTs. ABRs were measured in 1-, 3-, 6- and 9-mo old WT and DKO mice. (A–D) Representative ABR traces in response to 80 dB SPL sound clicks are shown for WT (black) and DKO (light grey), at ages 1-, 3-, 6- and 9-mo old as indicated. (E) Average waves I and II amplitudes (input/output, I/O) linear regression slope functions were determined for responses to sound clicks. Wave I, but not wave II, amplitudes were significantly reduced in DKO mice compared to WT mice in response to click sound in 1-mo old. In 3-mo old wave II was significantly different. The mean values for 1-mo old mice for wave I (I/O slope (μV/dB); mean ± SD) were; WT = 0.19 ±.0.04; DKO = 0.10 ± 0.04; n = 11; p < 0.0001. Mean wave II values were; WT = 0.60 ±.0.05; DKO = 0.61 ± 0.08; n = 11; p = 0.7. The mean values for 3-mo-old mice for wave I (I/O slope (μV/dB); mean ± SD) were; WT = 0.20 ±.0.05; DKO = 0.11 ± 0.04; n = 11; p < 0.0001. Mean wave II values were; WT = 0.61 ±.0.07; DKO = 0.50 ± 0.09; n = 11; p = 0.004. (F) Average waves I and II latency (input/output, I/O) functions versus sound clicks. Wave I latency I/O linear regression slopes were significantly different between WT and DKO mice. The mean values for 1-mo old mice for wave I latency (I/O slope (μs/dB); mean ± SD) were; WT = 8.60 ±.0.82; DKO = 11.05 ± 1.57; n = 11; p < 0.0002. Mean wave II values were; WT = 24.40 ±.5.01; DKO = 35.09 ± 4.02; n = 11; p = 0.0001. The mean values for 3-mo old mice for wave I (I/O slope (μV/dB); mean ± SD) were; WT = 10.73 ±.0.73; DKO = 18.93 ± 2.02; n = 11; p < 0.0001. Mean wave II values were; WT = 31.09 ±. 7.11; DKO = 35.80 ± 9.12; n = 11; p = 0.192. Additionally, the I/O slope (μV/dB) of wave I amplitude at 6-mos and 9-mos were; WT = 0.16 ± 0.05; DKO = 0.08 ± 0.06; n = 10; p = 0.005 and (9-mos); WT = 0.14 ± 0.08; DKO = 0.05 ± 0.02; n = 10; p = 0.04. The I/O slope (μs/dB) of wave I latency at 6-mos and 9-mos were; WT = 12.37 ± 0.91; DKO = 20.81 ± 3.11; n = 10; p < 0.0001 and (9-mos); WT = 13.21 ± 1.06; DKO = 22.63 ± 4.11; n = 10; p < 0.0001. (G) Mean absolute ABR thresholds in response to click stimulus were not statistically significantly different between WT and DKO mice in 1-3 mo old but were significantly different in 6- and 9-mo old mice. The mean values for ABR thresholds for 6-mo old were (dB SPL); WT = 24.44 ± 5.27; DKO = 57.22 ± 16.41; n = 9; p = 0.0002. Mean thresholds for or 9-mo old were; WT 46.25 ± 8.76; DKO = 83.13 ± 11.93; n = 8; p < 0.0001.