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

Abstract

[EN]Autism is an early-onset neurodevelopmental disorder characterized by restricted, repetitive behaviors and atypical patternsof social communication and interaction. A considerable proportion of autistic individuals experience divergent auditory per-ception, which can interfere with their ability to navigate everyday sound environments. Auditory brainstem responses areelectrophysiological 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 laten-cies than males. This sex-specific neurophysiological profile is especially relevant in autism research, where the male-to-femalediagnosis ratio is approximately 3:1. Thus, exploring the neurobiological mechanisms underlying sex-specific variations in autis-tic traits is essential. Furthermore, autism sensory profiles may vary based on the independent and mutual effects of environmen-tal 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 peakamplitudes and latencies (Waves I through V), inter-peak intervals (I–III, I–V, and III–V), and amplitude ratios (III:I, V:I, andV:III). Female rats generally exhibited greater amplitudes and longer latencies across waveforms. Regarding rat models, controlanimals consistently showed larger amplitudes and shorter latencies compared to autism-like models. Exploratory analyses fur-ther 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.