Deciphering the interplay between LPS/TLR4 pathways, neurotransmitter, and deltamethrin-induced depressive-like...

Area of Science:

• Environmental toxicology
• Neuroscience
• Microbiology

Background:

• Improper use of deltamethrin (DM) leads to accumulation in various environmental matrices and the human body.
• DM exposure is linked to neurotoxicity and behavioral abnormalities, but mechanisms are unclear.
• The gut-brain axis is increasingly recognized for its role in central nervous system (CNS) disorders.

Purpose of the Study:

• To investigate the role of the gut-brain axis in deltamethrin-induced behavioral anomalies in mice.
• To elucidate the mechanisms underlying DM-induced neurotoxicity and behavioral changes.

Main Methods:

• Mice were exposed to deltamethrin.
• Behavioral tests were conducted to assess depressive-like behavior.
• Hippocampal and gut tissues were analyzed for structural integrity and protein expression.
• Gut microbiota composition was analyzed using 16S rRNA sequencing.
• Fecal microbiota transplantation (FMT) was performed.

Main Results:

• DM exposure induced depressive-like behavior and disrupted hippocampal structure.
• Compromised gut barrier integrity was observed, with increased lipopolysaccharide (LPS) leakage.
• DM exposure altered neurotransmitter pathways, notably inhibiting 5-hydroxytryptamine (5-HT) production.
• Gut microbiota dysbiosis occurred, with specific bacteria correlating with behavioral and physiological changes.
• FMT experiments indicated that DM-induced gut dysbiosis contributes to depressive-like behavior.

Conclusions:

• Deltamethrin-induced neurotoxicity and behavioral changes are significantly mediated by the microbiota-gut-brain axis.
• Gut barrier disruption, inflammation, and alterations in gut microbiota composition are key mechanisms.
• Targeting the gut microbiota may offer a novel therapeutic strategy for deltamethrin toxicity.