m⁶A-Mediated Hippocampal BDNF Deficiency Contributes to Aflatoxin B1-Induced Neurotoxicity.

Area of Science:

• Neuroscience
• Toxicology
• Molecular Biology

Background:

• Aflatoxin B1 (AFB1) is a common contaminant in agricultural products with known neurotoxic effects.
• The specific molecular mechanisms underlying AFB1-induced neurotoxicity, particularly in the central nervous system (CNS), remain largely undefined.

Purpose of the Study:

• To investigate the impact of AFB1 on behavior and identify molecular pathways involved in its neurotoxic effects.
• To elucidate the role of brain-derived neurotrophic factor (BDNF) and RNA modification in AFB1-induced CNS injury.

Main Methods:

• Behavioral tests in mice to assess anxiety-like behavior and cognitive impairment.
• Hippocampal transcriptomics to analyze gene expression changes in neurons and astrocytes.
• In vitro studies using neuronal and astrocyte cultures.
• Investigation of m6A modification on BDNF mRNA using molecular biology techniques.

Main Results:

• AFB1 exposure induced anxiety-like behavior and cognitive deficits in mice.
• Neurons were more sensitive to AFB1 than astrocytes, with reduced BDNF secretion.
• AFB1 enhanced m6A modification on BDNF mRNA's 3'UTR in neurons, mediated by YTHDF2, leading to decreased BDNF expression.
• Administration of exogenous BDNF ameliorated AFB1-induced neurological disorders.

Conclusions:

• AFB1 induces CNS injury by downregulating BDNF expression through enhanced m6A modification.
• YTHDF2 plays a critical role in mediating AFB1's effect on BDNF mRNA.
• Targeting m6A modification presents a potential therapeutic strategy for AFB1-induced neurotoxicity.