1-Octen-3-ol exacerbates depression-induced neurotoxicity via the TLR4/NF-κB and Nrf2/HO-1 pathways.

1-Octen-3-ol is a volatile compound widely found in various fungi and plants, and studies have suggested its potential role in the development of neurodegenerative diseases. However, the mechanism by which 1-octen-3-ol induces neural injury in rats remains unclear. In this study, we used aerosolized 1-octen-3-ol to treat depressive model rats to investigate its effects on neural injury behaviors and neurophysiology in SD rats. The results showed that 1-octen-3-ol significantly increased the lung index to 0.47, reduced the sucrose preference rate to 42.9 %, decreased spontaneous exploration in the open field test, and increased immobility time in the forced swim test. Furthermore, 1-octen-3-ol disrupted blood-brain barrier permeability by reducing the expression of tight junction proteins Occludin and Claudin-1. It also promoted corticosterone secretion, reduced the release of monoamines (serotonin and norepinephrine) and amino acid neurotransmitters (5-hydroxytryptophan), and increased pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), leading to neuroendocrine damage. Additionally, it reduced the expression of synaptic proteins (PSD-95, Synapsin, and NMDA1) and neurotrophic factors (NT3 and NT4), resulting in impaired neuroplasticity. Simultaneously, 1-octen-3-ol activated the TLR4/NF-κB inflammatory pathway and suppressed the expression of the Nrf2/HO-1 antioxidant pathway, exacerbating neural injury in rats. These findings provide a mechanistic basis for the exacerbation of depression-induced neural injury by 1-octen-3-ol.