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

Efectos neurotóxicos de la exposición a nanoplásticos sobre el comportamiento similar a la depresión y la función cognitiva en ratones sometidos a estrés crónico leve impredecible.

• Dewei Chang School of Pharmacy, Department of Medicine, Hubei University of Science and Technology, Xianning City, Hubei Province, China. https://orcid.org/0009-0006-8282-9577
• Miao Xu Outpatient Department, West China Emei Hospital/ Mount Emei Jingchuan Hospital, Leshan City, Sichuan Province, P. R. China. https://orcid.org/0009-0008-0645-7243
• Wenning Shi School of Pharmacy, Department of Medicine, Hubei University of Science and Technology, Xianning City, Hubei Province, China. https://orcid.org/0009-0007-4977-4014
• Yan He Internal Medicine Department, The Second Affiliated Hospital, Hubei University of Science and Technology, Xianning City, Hubei Province, P. R. China. https://orcid.org/0009-0001-1725-3317
• Zhe Wu School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning City, Hubei Province, P. R. China. https://orcid.org/0009-0000-0465-8748
• Zhifeng Ning School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning City, Hubei Province, P. R. China. https://orcid.org/0000-0002-6700-161X
• Yanling Sun School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning City, Hubei Province, P. R. China. https://orcid.org/0009-0000-1301-3730
• Jianguo Lv Psychiatry Department, The Second Affiliated Hospital, Hubei University of Science and Technology, Xianning City, Hubei province, P. R. China. https://orcid.org/0009-0005-0674-4814

DOI: https://doi.org/10.54817/IC.v67n2a09

Keywords: Microplastics, Nanoparticles, Nanoplastic, BDNF/TrkB, Chronic unpredictable mild Stress, Depression-like behavior, Disease Models, Animal, Hippocampus

Abstract

The aim was to investigate the effects of gavage exposure to nanoplastics (NPs) on cognitive decline and depression-like behavior was investigated 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 factor (BDNF) and its receptor, the tyrosine kinase receptor B (TrkB), signaling pathway in the hippocampus of mice. Behavioral assessments included the sucrose preference test, the open field test, the forced swim test, and the Morris water maze. Nissl staining was used to assess hippocampal neuronal morphology. 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 preference, 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 control 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 conclusion, 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.

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