Neuroactive steroids as targets of micro- and nano-plastics: Putative impact on brain function and disease

: Among environmental pollutants, microplastics (MPs) and nanoplastics (NPs) represent a major threat to marine and terrestrial ecosystems because of their widespread distribution, environmental persistence, accumulation in animal and human organs, and toxicity. MPs and NPs target the major endocrine components, including the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, thus affecting steroid milieu with repercussions for peripheral endocrine glands and brain functions. Steroid hormones, either locally synthesized by neurons and glial cells, or reaching the brain from peripheral glands, exert neuroactive actions regulating neuronal excitability, neurogenesis, mood, and behavior. Despite numerous studies investigating the endocrine-disrupting effects of MPs/NPs and their potential reproductive toxicity, the implications of such effects on brain neuroactive steroids are poorly investigated. Here, we first illustrate how neuroactive steroids affect brain functions, then we review clinical and preclinical studies assessing the effects of MPs/NPs on neuroactive steroid levels, with the aim to understand putative implications for mental health.