Simms Shion S, Milani Marcus N, Kim Mi-Jung, Husain Ryan, Infante Laura, Cooke Paul S, Someya Shinichi
Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.
Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL, USA.
bioRxiv. 2024 Mar 6:2024.03.03.583163. doi: 10.1101/2024.03.03.583163.
Although estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) and knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight of KO females was lower than that of KO males. Body weight of KO females was higher than that of WT females, while there was no difference in body weight between WT and KO males. Similarly, head diameter was higher in KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT and KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance in KO mice. Taken together, our findings show that deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss of is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions.
尽管雌激素会影响神经系统和大脑的结构与功能,并且对认知有诸多作用,但其在听觉和前庭系统中的作用仍不明确。雌激素的作用主要通过两种经典的核雌激素受体介导,即雌激素受体1(ESR1)和雌激素受体2(ESR2)。在本研究中,我们使用3月龄的野生型(WT)和基因敲除(KO)小鼠(背景为CBA/CaJ,一种听力正常的品系),研究了ESR1在正常听觉功能和平衡能力中的作用。正如预期的那样,KO雌性小鼠的体重低于KO雄性小鼠。KO雌性小鼠的体重高于WT雌性小鼠,而WT和KO雄性小鼠的体重没有差异。同样,KO雌性小鼠的头部直径大于WT雌性小鼠。与我们的预期相反,在8、16、32和48kHz时,WT和KO小鼠的听觉脑干反应(ABR)阈值、ABR波I-V振幅和ABR波I-V潜伏期、8、16和32kHz时的畸变产物耳声发射(DPOAE)阈值和振幅以及转棒平衡能力(跌倒潜伏期)均无差异。此外,KO小鼠的ABR、DPOAE和转棒平衡能力不存在性别差异。综上所述,我们的研究结果表明,基因缺失并不影响听力正常小鼠的听觉功能或平衡能力,并提示在正常生理条件下,基因缺失可能由ESR2或其他雌激素受体代偿,以维持听觉和前庭系统的结构与功能。