Aspirin ameliorates the cognition impairment in mice following benzo[a]pyrene treatment via down-regulating BDNF IV methylation

• Published in: Neurotoxicology (Park Forest South) Vol. 89; pp. 20 - 30
• Main Authors: Li, Yangyang, Cao, Jingjing, Hao, Zhongsuo, Liu, Aixiang, Li, Xin, Li, Huan, Xia, Na, Wang, Zemin, Zhang, Zhihong, Bai, Jianying, Zhang, Hongmei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022; Elsevier BV
• Subjects: Animals; Apoptosis; Aspirin; Aspirin - metabolism; Aspirin - pharmacology; Benzo(a)pyrene; Benzo(a)pyrene - metabolism; Benzo(a)pyrene - toxicity; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cerebral cortex; Cognition; Cognitive ability; Cognitive Dysfunction - metabolism; Cognitive impairment; DNA Methylation; DNA methyltransferase; Drinking water; Hippocampus; Impairment; Inhibition (psychology); Mice; mRNA; Neurotoxicity; Prevention; Proteins; Pyrene; DNA methylation; Aspirin; Benzo[a]pyrene; Brain-derived neurotrophic factor; Cognitive impairment
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2021.12.008

•Benzo[a]pyrene can induce cognitive impairment in mice, however, the mechanism and intervention are not clear.•Brain-derived neurotrophic factor regulates neuronal survival, and learning and memory.•Inducing DNA hypermethylation of brain-derived neurotrophic factor is the molecular mechanism of neurotoxicity.•Aspirin is a promising primary prevention for the neurotoxicity of benzo[a]pyrene via down-regulating DNA methylation. Benzo[a]pyrene (B[a]P) is neurotoxic, however, the mechanisms remain unclear and there is no effective prevention. Available evidence suggests a role of DNA methylation in B[a]P-induced neurotoxicity. This study investigated the brain-derived neurotrophic factor (BDNF) IV methylation in the development of and aspirin intervention against B[a]P’s neurotoxicity in mice and HT22 cells. Mice were intraperitoneally treated with solvent or B[a]P (0.5, 2, and 10 mg/kg b.w.) for 60 days. An intervention group was treated simultaneously with B[a]P (10 mg/kg, i.p.) and aspirin (10 mg/kg, daily water-drinking). The treated mice showed a dose-dependent cognitive and behavioral impairment, and cerebral cell apoptosis, which were alleviated by aspirin co-treatment. Following B[a]P treatment, DNA methyltransferase (DNMTs) and BDNF IV hypermethylation were increased in the cerebral cortex of mice compared to controls, while significant decreases were found in BDNF IV and BDNF mRNA, and BDNF protein levels. Aspirin co-treatment rescued DNMTs activation and BDNF IV hypermethylation, and mitigated the recession in BDNF mRNA and protein induced by B[a]P treatment. Similar results were shown in HT22 cells. These findings reveal a critical role of BDNF IV methylation in the neurotoxicity of B[a]P, and demonstrate a promising prevention of aspirin against B[a]P-induced cognitive impairment via inhibiting BDNF IV hypermethylation.