Sex Differences in Auditory Brainstem Responses of Two Rat Models of Autism: Environmental and Genetic Contributions to Autism-Like Auditory Function

两种自闭症大鼠模型听觉脑干反应的性别差异:环境和遗传因素对自闭症样听觉功能的影响

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Abstract

Autism is an early-onset neurodevelopmental disorder characterized by restricted, repetitive behaviors and atypical patterns of social communication and interaction. A considerable proportion of autistic individuals experience divergent auditory perception, which can interfere with their ability to navigate everyday sound environments. Auditory brainstem responses are electrophysiological potentials elicited by auditory stimuli that evaluate neural activity along the auditory nerve and brainstem. Importantly, the auditory brainstem response varies by sex, with females typically showing higher amplitudes and shorter latencies than males. This sex-specific neurophysiological profile is especially relevant in autism research, where the male-to-female diagnosis ratio is approximately 3:1. Thus, exploring the neurobiological mechanisms underlying sex-specific variations in autistic traits is essential. Furthermore, autism sensory profiles may vary based on the independent and mutual effects of environmental and genetic factors. To deepen this understanding, we examined auditory brainstem responses in two rat models of autism: the GRIN2B rare mutation model and the prenatal valproic acid induction model, alongside control animals. We assessed peak amplitudes and latencies (Waves I through V), inter-peak intervals (I-III, I-V, and III-V), and amplitude ratios (III:I, V:I, and V:III). Female rats generally exhibited greater amplitudes and longer latencies across waveforms. Regarding rat models, control animals consistently showed larger amplitudes and shorter latencies compared to autism-like models. Exploratory analyses further suggested pairwise interactions between sex and rat model, indicating modulation of auditory phenotypes linked to autism. Thus, our findings reveal key insights into the effects of sex and rat model, as well as their interactions.

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