Antidepressant-like effects of L-menthol mediated by alleviating neuroinflammation and upregulating the BDNF/TrkB signaling pathway in subchronically lipopolysaccharide-exposed mice

Abstract

L-menthol (LM) is a safe and bioactive monoterpenoid from Mentha haplocalyxBriq., with which an acute treatment has shown significant antidepressant-like effects potentially mediated by the modification of monoamine system in mice. Nonetheless, the above conclusions were all based on the forced swimming test. The antidepressant-like effects of acute and subchronic administrations with LM on other depression models have never been illuminated, and its potential mechanisms require further explorations. In this study, the antidepressant-like effects and potential mechanisms of an acute treatment with LM were validated through behavioral despair tests, reserpine-induced ptosis, akinesia and hypothermia test, and 5-hydroxytryptophan-induced head-twitch test in mice. The antidepressant-like effects of subchronic treatments with LM were evaluated in a modified lipopolysaccharide (LPS)-induced depression model. Furthermore, the effects of subchronic treatments with LM on the microglial activation, hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling pathway in LPS-induced mice were detected through immunofluorescence assay, enzyme-linked immunosorbent assay and western blotting analysis. Our results showed that acute and subchronic administrations with LM exerted significant antidepressant-like effects in different depression models, which might be mediated by modulating the monoamine system, alleviating neuroinflammation and upregulating the BDNF/TrkB signaling pathway in mice. Taken together, the current study systematically explored the potential of LM as a new candidate for depression therapy, and provided a modified LPS-induced depression model with better apparent and predictive validity.