Exposure to polystyrene nanoplastics causes anxiety and depressive-like behavior and down-regulates EAAT2 expression in mice.

Abstract

Microplastics exposure can induce brain dysfunction like cognitive impairment, Parkinson's disease, and autism spectrum disorders. In this study, we aimed to investigate the effects of Polystyrene nanoplastics (NPS) on anxiety and depression in mice. First, Polystyrene nanoplastics (NPS) (10 mg/kg) were administered orally daily for two months starting at PND 21. Subsequently, behavioral tests about anxiety and depression were conducted, including the open field test, the elevated plus maze, the forced swimming test, and the tail suspension test. The results showed that NPS induced anxiety and depression-like behaviors in mice. The mPFC played a pivotal role in the etiology of anxiety and depression, in which nanoplastics led to impaired synaptic transmission and reduced neuronal activity in vivo in mPFC. Furthermore, the astrocyte marker GFAP was abnormally increased as observed in mPFC. The abnormal activation of astrocytes results in impaired glutamate recycling through decreasing the expression of the glutamate transporter protein EAAT2 after NPS exposure. In order to ascertain the function of EAAT2, the EAAT2 activator (LDN-212320) was employed to stimulate the expression of EAAT2. Following the activation of EAAT2, synaptic transmission, and anxiety and depressive behavior were rescued in the mice. Polystyrene nanoplastics induce anxiety and depressive-like behavior in mice possibly inhibiting astrocyte EAAT2 expression. Specific activation EAAT2 of astrocytes rescue anxiety and depressive behavior in nanoplastics exposed mice.