Killer or helper? The mechanism underlying the role of adenylate activated kinase in sound conditioning.
Killer or helper? The mechanism underlying the role of adenylate activated kinase in sound conditioning.
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DOI：
10.3389/fnsyn.2022.940788
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发表时间：
2022
影响因子：
3.7
通讯作者：
Yu, Ning
中科院分区：
文献类型：
--
作者：
Zhao, Rui;Ma, Changhong;Wang, Minjun;Li, Xinxin;Liu, Wei;Shi, Lin;Yu, Ning
目的：探讨声适应是否通过激活腺苷酸活化激酶(AMPK)来影响听觉系统的保护，以及这种适应是否能保护突触免受高强度噪声的伤害。12周龄CBA小鼠随机分为4组，每组24只：对照组、声适应(SC)组、声适应+噪声暴露(SC+NE)组和噪声暴露(NE)组。分别在测试前、噪声调节后、暴露后0、3、7、14天进行听阈评估。分别在实验前、条件反射后、暴露后0d和14d检测90分贝强度下I波的波幅和潜伏期。免疫荧光染色检测突触数目和AMPK活性，免疫印迹法检测p-AMPK蛋白表达。听性脑干反应(ABR)阈值在SC组和对照组之间无显著差异。110d B噪声暴露后，两个SC组动物的听力损失程度均明显低于NE组。SC组动物恢复正常阈值较快，65dBSPL声适应具有更强的听觉保护作用。声适应后，SC组ABR I波波幅高于对照组。噪声暴露后即刻(D0)，各组ABR I波波幅均显著降低，以去甲肾上腺素组下降最显著，65SC+NE组显著高于85SC+NE组。SC组I波潜伏期明显短于对照组。D0时，NE组较对照组潜伏期延长。而65SC+NE组和85SC+NE组的潜伏期无显著差异。此外，在d14，NE组和对照组之间没有显著差异，而65SC+NE组和85SC+NE组的潜伏期仍然显著短于对照组。SC小鼠的带状突触数目与对照组无显著差异。110d B噪声暴露后，SC+NE组的带状突触明显多于NE组。噪声暴露14d后，各组大鼠突触均恢复正常，但SC组的恢复时间明显短于非SC组(p<；0.05)。110dB噪声暴露后，NE组蛋白表达最强，SC+NE组次之，对照组蛋白表达最低。声音条件化动物比非SC动物具有更强的抗噪能力，听力恢复更快。此外，65dBSPL SC比85dBSPL SC提供了更好的听力保护。早期激活AMPK可能通过增加ATP储存和减少大量p-AMPK的释放来保护听力，从而有助于抑制突触损伤。
To investigate whether sound conditioning influences auditory system protection by activating adenylate activated kinase (AMPK), and if such adaption protects ribbon synapses from high-intensity noise exposure. CBA mice (12 weeks old) were randomly divided into four groups (n = 24 mice per group): control, sound conditioning (SC), sound conditioning plus noise exposure (SC+NE), and noise exposure (NE). Hearing thresholds were assessed before testing, after sound conditioning, and 0, 3, 7, and 14 days after 110 dB noise exposure. Amplitudes and latencies of wave I at 90 dB intensity were assessed before test, after conditioning, and at 0 and 14 days after 110 dB noise exposure. One cochlea from each mouse was subjected to immunofluorescence staining to assess synapse numbers and AMPK activation, while the other cochlea was analyzed for phosphorylated adenylate activated kinase (p-AMPK) protein expression by western blot. There was no significant difference in auditory brainstem response (ABR) threshold between SC and control mice. The degree of hearing loss of animals in the two SC groups was significantly reduced compared to the NE group after 110 dB noise exposure. Animals in the SC group showed faster recovery to normal thresholds, and 65 dB SPL sound conditioning had a stronger auditory protection effect. After sound conditioning, the amplitude of ABR I wave in the SC group was higher than that in the control group. Immediately after noise exposure (D0), the amplitudes of ABR I wave decreased significantly in all groups; the most significant decrease was in the NE group, with amplitude in 65SC+NE group significantly higher than that in the 85SC+NE group. Wave I latency in the SC group was significantly shorter than that in the control group. At D0, latency was prolonged in the NE group compared with the control group. In contrast, there was no significant difference in latency between the 65SC+NE and 85SC+NE groups. Further, at D14, there was no significant difference between the NE and control groups, while latency remained significantly shorter in the 65SC+NE and 85SC+NE groups compared with controls. Number of ribbon synapses in SC mice did not differ significantly from that in controls. After 110 dB noise exposure, there were significantly more ribbon synapses in the SC+NE group than the NE group. Ribbon synapses of all groups were recovered 14 days after the noise exposure, while the SC group had a shorter recovery time than the non-SC groups (p < 0.05). AMPK was highly activated in the SC group, and p-AMPK expression was detected; however, after 110 dB noise exposure, the strongest protein expression was detected in the NE group, followed by the SC+NE groups, and the lowest protein expression was detected in the control group. Sound conditioning animals were more noise resistant and recovered hearing faster than non-SC animals. Further, 65 dB SPL SC offered better hearing protection than 85 dB SPL SC. Early AMPK activation may protect hearing by increasing ATP storage and reducing the release of large quantities of p-AMPK, which could help to inhibit synapse damage.
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DOI：
10.1523/jneurosci.5027-12.2013
发表时间：
2013-03-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Maison SF;Usubuchi H;Liberman MC
通讯作者：
Liberman MC
影响因子：
2.8
作者：
Hu, BH;Zheng, XY;Henderson, D
通讯作者：
Henderson, D
DOI：
10.1073/pnas.1222295110
发表时间：
2013-04-30
影响因子：
11.1
作者：
Housley, Gary D.;Morton-Jones, Rachel;Ryan, Allen F.
通讯作者：
Ryan, Allen F.
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
二甲双胍可减轻小鼠大脑中动脉闭塞后血脑屏障的破坏
影响因子：
9.3
作者：
Liu Y;Tang G;Li Y;Wang Y;Chen X;Gu X;Zhang Z;Wang Y;Yang GY
通讯作者：
Yang GY