Neurotoxic effects of nanoplastics exposure on depression-like behavior and cognitive function in mice under chronic unpredictable mild stress.

The aim was to investigate the effects of gavage exposure to nanoplastics (NPs) on cognitive decline and depression-like behavior was in-vestigated in mice subjected to chronic unpredictable mild stress (CUMS). BALB/c mice were randomly assigned to four experimental groups: Control (Ctrl), nanoplastics (NPs), Mod (subjected to CUMS), and NPs+Mod (nano-plastics + CUMS). We evaluated the role of the brain-derived neurotrophic fac-tor (BDNF) and its receptor, the tyrosine kinase receptor B (TrkB), signaling pathway in the hippocampus of mice. Behavioral assessments included the su-crose preference test, the open field test, the forced swim test, and the Morris water maze. Nissl staining was used to assess hippocampal neuronal morphol-ogy. BDNF and TrkB mRNA levels and protein expression in the hippocampus were measured by qPCR and Western blotting, respectively. Mice in the NPs, Mod, and NPs+Mod groups showed reduced body weight, lower sucrose pref-erence, poorer performance in the open field test, and prolonged immobility in the forced swim test. Additionally, there was a reduction in hippocampal neurons and deficits in spatial learning and memory compared with the con-trol group. BDNF mRNA and TrkB protein levels were decreased. Compared with the Mod group, the NPs+Mod group exhibited increased depression-like behaviors and cognitive impairments, greater hippocampal neuronal damage, and further reductions in BDNF and TrkB mRNA and protein levels. In conclu-sion, NP exposure has neurotoxic properties that can exacerbate CUMS-induced depression-like behavior and cognitive deficits, likely by further suppressing the hippocampal BDNF/TrkB signaling pathway.