Autism spectrum disorder (ASD) is a neurodevelopmental condition with a prevalence rate of 2.78%, and it is characterized by deficits in sociability and communication and restricted patterns of interests and activities. Remarkably, this psychiatric disorder exhibits a pronounced gender bias, with 80% of children diagnosed with ASD being boys. In this review, we will present advancements in mouse models of ASD and their potential contributions to our understanding of the disorder. We will highlight how initial pre-clinical investigations focused solely on male mice due to the gender bias in ASD and explain why we believe that this approach might have had detrimental consequences regarding our understanding of ASD etiology and pathophysiology. We will highlight the evidence of two sensitive periods during brain development when differential exposure to gonadal hormones may result in sex differences in brain function and behavior: the perinatal period and the pre-pubertal period. Finally, we will suggest neuroinflammation as a feasible biological mechanism that may converge different ASD etiological factors and cellular mechanisms into a brain sexual differentiation context, thus accounting for the gender disparities observed in the disorder.

Light pollution is a major anthropogenic environmental change and a significant threat to ecosystems. Among other detrimental effects on physiology, artificial light at night (ALAN) disrupts circadian rhythms in a wide range of species. However, the underlying neuronal and genetic mechanisms remain poorly understood. Here, we show in Drosophila that the loss of the circadian clock gene period exacerbates the ALAN-induced shift towards nocturnal behaviour, with a more pronounced effect on males. In contrast, the loss of cycle has no such effect on males or females; cyc null mutants are nocturnal under standard light‒dark cycles, and their activity and sleep profiles are minimally or not affected by ALAN exposure. CRISPR-Cas9 knockout of period in most clock neurons resembles the null mutant phenotype. Our results show that mutations in components of the positive and negative limbs of the circadian clock result in distinct responses to nocturnal light and highlight the role of genetic factors in modulating behavioural plasticity in response to environmental perturbations.