1.400038 重庆,陆军军医大学(第三军医大学)基础医学院神经生物学教研室
2.530004 南宁,广西大学脑与智能研究中心
3.857000 西藏 日喀则,陆军第953医院外科
Received:07 July 2021,
Revised:2021-08-23,
Published:30 January 2022
移动端阅览
Sumei YAN, Shaowen QIAN, Xianli HU, et al. Auditory brainstem responses during development of MeCP2 autistic mice[J]. Journal of Army Medical University, 2022, 44(2): 103-109.
Sumei YAN, Shaowen QIAN, Xianli HU, et al. Auditory brainstem responses during development of MeCP2 autistic mice[J]. Journal of Army Medical University, 2022, 44(2): 103-109. DOI: 10.16016/j.2097-0927.202107039.
目的
2
探索甲基-CpG结合蛋白2(methyl CpG binding protein 2
MeCP2)过表达小鼠(MeCP2-Tg1,自闭模型小鼠)发育过程中的听力变化。
方法
2
在8周和14周对MeCP2-Tg1小鼠(Tg1组)和WT小鼠(WT组)进行三箱社交行为测试,检测MeCP2-Tg1小鼠的社交功能。在社交行为异常发生前后的5个发育节点(4、8、12、16、20周)记录click及纯音刺激诱发的听觉脑干电位,评估不同发育阶段Tg1小鼠的听力敏感性(阈值)、神经传导速度(潜伏期)和反应强度(波幅)。
结果
2
①与WT组相比,Tg1组小鼠在4周和12周对24 kHz纯音刺激表现出更高的敏感性(
P
<
0.05),20周时对8 kHz纯音刺激表现出更低的阈值(
P
<
0.05),但阈值降低现象在发育进程中并不持续。②Tg1组小鼠在整个发育过程中的神经传导速度正常。③与WT组相比,Tg1组小鼠表征上橄榄核的Ⅲ波幅值在8周(含)之前正常,但12周(含)之后表现出显著的持续性升高(
P
<
0.05);表征听觉下丘的Ⅴ波幅值在8周(含)之前显著偏低(
P
<
0.05),但12周及之后则恢复正常。
结论
2
MeCP2-Tg1小鼠听觉脑干反应在发育过程中出现异常,主要表现为在不同发育时期对声刺激反应幅度的增高/降低,且听力异常的发生早于社交行为异常发生。
Objective
2
To explore the hearing changes in an autism model mice [MeCP2-Tg1 mice
with overexpression of methyl-CpG binding protein 2 (MeCP2)] during development.
Methods
2
Three-chamber social test was used to assess the social ability of MeCP2-Tg1 mice and wild-type mice at 8 and 14 weeks after born. Auditory brainstem responses evoked by click and pure tone stimulus were recorded at 5 development nodes (4
8
12
16 and 20 weeks) before and after the onset of abnormal social behaviors to assess hearing sensitivity (threshold)
neural conduction velocity (latency) and response level (amplitude) in MeCP2-Tg1 mice at different developmental stages.
Results
2
①Tg1 mice showed higher sensitivity to 24 kHz stimulus at 4 and 12 weeks (
P
<
0.05)
and lower hearing threshold to 8 kHz stimulus at 20 weeks as compared with wild-type mice (
P
<
0.05)
but the threshold reduction did not persist over the course of development. ②Tg1 mice had normal neural conduction velocity throughout development. ③ Compared with the wild-type mice
the amplitude of wave Ⅲ
which characterizes the superior olivary complex
was normal up to 8 weeks (inclusive) but showed a significant an
d persistent increase after 12 weeks (inclusive) (
P
<
0.05); the amplitude of wave V
which characterizes the auditory inferior colliculus
was significantly lower up to 8 weeks (inclusive) (
P
<
0.05) but showed normal after 12 weeks (inclusive).
Conclusion
2
The auditory brainstem responses of MeCP2-Tg1 mice are abnormal during development
mainly in the form of increased/decreased amplitude of responses to acoustic stimuli at different developmental periods
and the onset of hearing abnormalities precedes the onset of social behavior abnormalities.
LEEKAM S R, NIETO C, LIBBY S J, et al . Describing the sensory abnormalities of children and adults with autism[J ] . J Autism Dev Disord, 2007, 37(5): 894-910. DOI: 10.1007/s10803-006-0218-7.
SINCLAIR D, ORANJE B, RAZAK K A, et al . Sensory processing in autism spectrum disorders and fragile X syndrome-from the clinic to animal models[J ] . Neurosci Biobehav Rev, 2017, 76(pt b): 235-253. DOI: 10.1016/j.neubiorev.2016.05.029.
ROBERTSON C E, BARON-COHEN S. Sensory perception in autism[J]. Nat Rev Neurosci, 2017, 18(11): 671-684. DOI: 10.1038/nrn.2017.112.
YU L D, WANG S P. Aberrant auditory system and its developmental implications for autism[J]. Sci China Life Sci, 2021, 64(6): 861-878. DOI: 10.1007/s11427-020-1863-6.
ROTSCHAFER S E. Auditory discrimination in autism spectrum disorder[J]. Front Neurosci, 2021, 15: 651209. DOI: 10.3389/fnins.2021.651209.
CHEUNG P P P, LAU B W M. Neurobiology of sensory processing in autism spectrum disorder[J]. Prog Mol Biol Transl Sci, 2020, 173: 161-181. DOI: 10.1016/bs.pmbts.2020.04.020.
MATSUZAKI J, KU M, DIPIERO M, et al . Delayed auditory evoked responses in autism spectrum disorder across the life span[J ] . Dev Neurosci, 2019, 41(3/4): 223-233. DOI: 10.1159/000504960.
MIRON O, ARI-EVEN ROTH D, GABIS L V, et al . Prolonged auditory brainstem responses in infants with autism[J ] . Autism Res, 2016, 9(6): 689-695. DOI: 10.1002/aur.1561.
TRUONG D T, RENDALL A R, CASTELLUCCIO B C, et al . Auditory processing and morphological anomalies in medial geniculate nucleus of Cntnap2 mutant mice[J ] . Behav Neuro-sci, 2015, 129(6): 731-743. DOI: 10.1037/bne0000096.
LIAO W, GANDAL M J, EHRLICHMAN R S, et al . MeCP2+/-mouse model of RTT reproduces auditory phenotypes associated with Rett syndrome and replicate select EEG endophenotypes of autism spectrum disorder[J ] . Neuro-biol Dis, 2012, 46(1): 88-92. DOI: 10.1016/j.nbd.2011.12.048.
ROTSCHAFER S E, MARSHAK S, CRAMER K S. Deletion of Fmr1 alters function and synaptic inputs in the auditory brainstem[J]. PLoS One, 2015, 10(2): e0117266. DOI: 10.1371/journal.pone.0117266.
GUY J, CHEVAL H, SELFRIDGE J, et al . The role of MeCP 2 in the brain[J ] . Annu Rev Cell Dev Biol, 2011, 27: 631-652. DOI: 10.1146/annurev-cellbio-092910-154121..
SANDWEISS A J, BRANDT V L,ZOGHBI H Y. Advances in understanding of Rett syndrome and MECP 2 duplication syndrome: prospects for future therapies[J ] . Lancet Neurol, 2020, 19(8): 689-698. DOI: 10.1016/s1474-4422(20)30217-9.
CHAO H T, ZOGHBI H Y, ROSENMUND C. MeCP 2 controls excitatory synaptic strength by regulating glutamatergic synapse number[J ] . Neuron, 2007, 56(1): 58-65. DOI: 10.1016/j.neuron.2007.08.018.
SUN L, CHEN R G, LI L, et al . Visualization and correction of social abnormalities-associated neural ensembles in adult MECP 2 duplication mice[J ] . Sci Bull, 2020, 65(14): 1192-1202. DOI: 10.1016/j.scib.2020.03.026..
TALGE N M, TUDOR B M, KILENY P R. Click-evoked auditory brainstem responses and autism spectrum disorder: a meta-analytic review[J]. Autism Res, 2018, 11(6): 916-927. DOI: 10.1002/aur.1946.
KALBASSI S, BACHMANN S O, CROSS E, et al . Male and female mice lacking neuroligin-3 modify the behavior of their wild-type littermates[J ] . eNeuro, 2017, 4(4): ENEURO. 0145-ENEURO. 0117.2017. DOI: 10.1523/ENEURO.0145-17.2017.
ZHANG D H, YU B, LIU J, et al . Altered visual cortical processing in a mouse model of MECP 2 duplication syndrome[J ] . Sci Rep, 2017, 7(1): 6468. DOI: 10.1038/s41598-017-06916-3..
HACOHEN-KLEIMAN G, YIZHAR-BARNEA O, TOULOUMI O, et al . Atypical auditory brainstem response and protein expression aberrations related to ASD and hearing loss in the adnp haploinsufficient mouse brain[J ] . Neurochem Res, 2019, 44(6): 1494-1507. DOI: 10.1007/s11064-019-02723-6.
SHI L J, CHANG Y, LI X W, et al . Cochlear synaptopathy and noise-induced hidden hearing loss[J ] . Neural Plast, 2016, 2016: 6143164. DOI: 10.1155/2016/6143164.
周畅. MECP2自闭症小鼠听觉异常及其皮层机制[D]. 重庆: 陆军军医大学, 2019.
ZHOU C. Auditory abnormalities and cortical mechanisms in MECP 2 autistic mice[D ] . Chongqing: Army Medical University, 2019.
PIERCE K, GAZESTANI V H, BACON E, et al . Evaluation of the diagnostic stability of the early autism spectrum disorder phenotype in the general population starting at 12 months[J ] . JAMA Pediatr, 2019, 173(6): 578-587. DOI: 10.1001/jamapediatrics.2019.0624.
0
Views
0
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621
