Neurobiological alterations and autism-like phenotype in mice following regulatory-limit exposure to fungicides in drinking water

Abstract

Neurodevelopmental conditions, including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), have increased markedly over recent decades. This rise parallels the widespread use of agrochemicals, suggesting a contribution of environmental exposures. We hypothesize that pesticide residues may disrupt brain development and promote neurodevelopmental disorders. Here, we test whether concentrations permitted in drinking water affect brain development using a maternal exposure model in wild-type mice. Exposure to a fungicide mixture at 0.3 g/L, below the current European regulatory limit of 0.5 g/L, impairs corticogenesis and is associated with alterations in synaptic function and glutamatergic signaling. Offspring exhibit delays in sensory development, reduced social interactions, and increased stereotyped behaviors. We identify the adenosine A2A receptor as a molecular target of anilinopyrimidine fungicides. Together, these findings indicate that low-dose exposure to this fungicide mixture can induce an autism spectrum-like phenotype in the offspring.