Adulthood bisphenol A exposure induces anxiety in male mice via downregulation of alpha-1D adrenergic receptor in paraventricular thalamus

Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical, is widely used in household plastic products. Large amounts of evidence indicate prenatal and postnatal BPA exposure causes neurodevelopmental disorders such as anxiety and autism. However, the neuronal mechanisms underlying the neurotoxic effects of adulthood BPA exposure remain poorly understood. Here, we provided evidences that adult mice treated with BPA (0.45 mg/kg/day) during 3 weeks exhibited sex-specific anxiety like behaviors. We demonstrated that the BPA-induced anxiety in male mice, but not in female mice, was closely associated with hyperactivity of glutamatergic neurons in the paraventricular thalamus (PVT). Acute chemogenetic activation of PVT glutamatergic neurons caused similar effects on anxiety as observed in male mice exposed to BPA. In contrast, acute chemogenetic inhibition of PVT glutamatergic neurons reduced BPA-induced anxiety in male mice. Concomitantly, the BPA-induced anxiety was related with a down-regulation of alpha-1D Adrenergic Receptor in the PVT. Taken together, the present study indicated a previously unknown target region in the brain for neurotoxic effects of BPA on anxiety and implicated a possible molecular mechanism of action.

Alpha-1D adrenergic receptor; Anxiety; Bisphenol A; Neurotoxicity; Paraventricular thalamus.