Ouagazzal Abdel-Mouttalib, Reiss David, Romand Raymond
IGBMC, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch, France.
Behav Brain Res. 2006 Sep 25;172(2):307-15. doi: 10.1016/j.bbr.2006.05.018. Epub 2006 Jun 30.
The present study examined the developmental course of the age-related hearing loss and its consequences on the expression of acoustic startle reflex (ASR) and prepulse inhibition (PPI) generated by white-noise bursts in 129S2/SvPas (129) and C57BL/6J (C57) mouse strains and their F(1) hybrids. Auditory brainstem responses (ABR), ASR and PPI were assessed at various time points: 6, 28, 41 and 94 weeks. Both parental strains showed marked ABR threshold shifts with age, with C57 mice having the most pronounced deficits. By contrast, the hybrids displayed only minor hearing loss with age. The time courses of ASR and PPI varied considerably between the mouse strains. From 6 to 41 weeks of age, ASR and PPI elicited by weak stimuli (70-90dB) increased in C57 mice, whereas the startle responses to intense stimuli (95-120dB) declined progressively. In 129 and hybrid mice, PPI levels remained relatively stable during the first year, but a progressive increase of ASR was observed in the hybrids for intense stimuli (95-120dB). When animals reached 94 weeks of age, marked deterioration of ASR was observed in all strains, while deficits in PPI were only seen in 129 and C57 mice. These findings show that the time course and the severity of the hearing loss vary considerably between 129, C57 strains and their hybrids, thus suggesting a marked heterogeneity in the genetic mechanisms underlying deafness in mice. They also demonstrate that the age-related hearing loss may have complex consequences on auditory behavioral performances depending of the severity of the deficits, the genetic background as well as the stimuli parameters.
本研究考察了129S2/SvPas(129)和C57BL/6J(C57)小鼠品系及其F1杂种中与年龄相关的听力损失的发展过程,以及白噪声猝发所产生的听觉惊吓反射(ASR)和前脉冲抑制(PPI)表达的后果。在不同时间点评估听觉脑干反应(ABR)、ASR和PPI:6周、28周、41周和94周。两个亲本品系均显示出随年龄增长ABR阈值显著变化,C57小鼠的缺陷最为明显。相比之下,杂种小鼠随年龄增长仅表现出轻微的听力损失。小鼠品系之间ASR和PPI的时间进程差异很大。在6至41周龄期间,C57小鼠中由弱刺激(70 - 90dB)引发的ASR和PPI增加,而对强刺激(95 - 120dB)的惊吓反应逐渐下降。在129小鼠和杂种小鼠中,第一年PPI水平保持相对稳定,但在杂种小鼠中观察到对强刺激(95 - 120dB)的ASR逐渐增加。当动物达到94周龄时,所有品系均观察到ASR明显恶化,而仅在129和C57小鼠中出现PPI缺陷。这些发现表明,129、C57品系及其杂种之间听力损失的时间进程和严重程度差异很大,从而提示小鼠耳聋潜在遗传机制存在明显的异质性。它们还表明,与年龄相关的听力损失可能根据缺陷的严重程度、遗传背景以及刺激参数对听觉行为表现产生复杂的影响。