Dioxin exposure is reported to affect nervous system development and increase the risk of neurodegenerative diseases. Generally, dioxin exerts its neurotoxicity via aryl hydrocarbon receptor (AhR). Neurofilament (NF) light (NFL) protein is a biomarker for both neuronal differentiation and neurodegeneration and its expression is controlled by the mitogen-activated protein kinase (MAPK) pathway. However, the effects of dioxin on NFL expression and involved mechanisms are incompletely understood. We aimed to investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on NFL expression and elucidate the underlining signaling pathways and their potential crosstalk, specifically between MAPK and AhR pathway. We employed primary cultured rat cortical neurons to evaluate the effect of TCDD exposure on NFL expression. We also used nerve growth factor (NGF)-treated PC12 cells with specific inhibitors to investigate the involvement of and potential crosstalk between the MAPK pathway and the AhR pathway in mediating the effects of TCDD on NFL expression. After TCDD exposure, NFL mRNA and protein levels were upregulated in cultured neurons. NFL protein was preferentially found in the cell body compared with neurites of the cultured neurons. In PC12 cells, TCDD enhanced both NGF-induced NFL expression and phosphorylation of ERK1/2 and p38. The addition of MAPK-pathway inhibitors (PD98059 and SB230580) partially blocked the TCDD-induced NFL upregulation. CH223191, an AhR antagonist, reversed the upregulation of NFL and phosphorylation of ERK1/2 and p38 induced by TCDD. This study demonstrated TCDD-induced upregulation of NFL in cultured neurons, with protein retained in the cell body. TCDD action was dependent on activation of AhR and MAPK, while crosstalk was found between these two signaling pathways.

Extreme high temperatures in the summer have become a global concern, and their risks to the inflammatory system have been largely unknown. Here we appraised the exposure risks of summer heatwaves by comparing the sera cytokine levels in healthy individuals under high and normal temperatures. In addition, we established a cell model with a 1.5 °C temperature increase to investigate the regulatory mechanisms of temperature-related cytokines. Our results suggest that elevated temperatures enhance the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) via the aryl hydrocarbon receptor (AhR) pathway and augment the pro-inflammatory effects of other factors. This suggests that we may have underestimated the impact of high temperatures on the health of individuals beyond just mortality rates. Moreover, seemingly minor temperature increases of just 1.5 °C can still pose a challenge to cells.

Background: Acori Tatarinowii Rhizome (ATR) is a well-recognized Chinese herbal medicine prescribed to treat neurological disorders. The essential oil (ATEO) is considered as the active fraction of ATR and the content of ATEO is used as the only indicator for ATR content determination. The quality of ATEO varies widely due to region difference; however, little is known about how to study ATEO quality chemically and biologically in response to region difference. Thus, it is of great importance to identify volatile active components in ATEO to conduct quality study. In this study, we analyzed ATEO from different regions in China using chemical component analysis combined with biological activity evaluation.Methods: GC-MS was used to obtain different volatile component profiles of ATEO and significantly changed volatile components were screened out. The neuroprotective activities of ATEO, including anti-oxidation, anti-inflammation and neurotrophic functions, were revealed in C6 glioma cells. The correlation study between the bioactivities and the components was performed.Results: 57 volatile components, including terpenoids, phenylpropanoids, aromatic compounds, and other aliphatic compounds, were identified. 8 volatile components (β-asarone, cis-methyl isoeugenol, γ-asarone, methyleugenol, calarene, longifolene, β-caryophyllene and caryophyllene oxide) from ATEO were significantly changed due to region difference and 2 of them (β-asarone and γ-asarone) showed strong correlation with neuroprotective activities.Conclusions: Our results reveal that ATEO from different regions in China show great changes in chemical composition and biological activity. Moreover, phenylpropanoids (β-asarone and γ-asarone) present strong correlation with the bioactivities, which are considered as volatile active components in ATEO. The findings will be useful for the development of quality study of ATEO.

1,3,6,8-Tetrabromocarbazole (1368-BCZ) is identified as an emerging contaminant that exerts angiogenic effects. Multiple studies indicated there was a positive correlation between angiogenesis and nuclear factor kappa B (NF-κB) activation. While the role of NF-κB in inflammation and apoptosis has been well known, the potential biological effects of 1368-BCZ on NF-κB signaling and related mechanism remain unclear. We, therefore, explored the possible effects of 1368-BCZ on the NF-κB pathway at the gene and protein levels and confirmed that NF-κB activation by 1368-BCZ exposure caused an augmented phosphorylated protein level, induction of NF-κB response element (κBRE)-driven luciferase activity and upregulation of transcriptional level of downstream responsive genes. Although 1368-BCZ did not produce detectable changes in hepatic fibrosis in vivo, it obviously altered the apoptosis in human hepatocellular carcinoma (HepG2) cells. Furthermore, the induction of apoptosis was confirmed by the increased cleaved caspase-3 level. These data revealed the activating effects of 1368-BCZ on NF-κB and its involvement in the underlying mechanisms, providing additional information for toxicology studies of emerging contaminants and introducing a mechanism-based toxicological evaluation of emerging pollutants.

Astrocytes play an important role in the nervous system's response to external stimulation. Environmental pollutants could activate astrocytes into A1 (toxic) or A2 (protective) types and induce different effects. Meanwhile, the aryl hydrocarbon receptor (AhR) is an environmental molecule sensor in the body and has various ligands. But the difference between exogenous and endogenous AhR ligands on the astrocytic activation is unclear; in this study, we employed rat primary cultured cortical astrocytes to reveal the effects and mechanisms of AhR ligands on astrocytic activation. We found that, after treatment with exogenous AhR ligand (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) ranging from 0.01 to 0.1 nmol/L, astrocytes mainly exhibited A2 type activation. The specific manifestation includes the increase in the expression of A2 marker genes, the enhancement of cellular autonomous movement, the expression and secretion of chemokines, such as Cxcl10, Cxcl2, and Ccl7. And TCDD-induced A2 type astrocytes show a positive impact on neuronal synaptic formation. Although both TCDD and endogenous AhR ligand (6-formylindolo[3,2-b] carbazole, FICZ) could activate AhR pathway in astrocytes, FICZ (50 nmol/L) neither induces activation of A2 type astrocytes nor upregulation of chemokines. Therefore, our findings suggest that AhR is crucial for astrocytes to recognize environmental pollutants and protect the nervous system.