Hippocampal Proteomics Reveals the Role of Glutamatergic Synapse Activation in the Depression Induced by Perfluorooctane Sulfonate.

Perfluorooctane sulfonate (PFOS), a new type of persistent organic pollutant in the environment of water, has drawn significant attention in recent years due to its widespread prevalence and high toxicity. Neurotoxicity is regarded as one of the major toxic effects of PFOS, while research studies on PFOS-induced depression and the underlying mechanisms remain scarce. In this study, behavioral tests revealed the depressive-like behaviors in PFOS-exposed male mice. Neuron damages including pyknosis and staining deepening were identified through hematoxylin and eosin staining. Then, we noticed the elevation of glutamate and proline levels as well as the decline of glutamine and tryptophan levels. Proteomics analysis identified 105 differentially expressed proteins that change in a dose-dependent manner and revealed that PFOS exposure activated the glutamatergic synapse signaling pathway, which were further confirmed by Western blot, and the data were consistent with the findings of the proteomics analysis. Additionally, the downstream signaling cyclic AMP-responsive element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and synaptic plasticity-related postsynaptic density protein 95, synaptophysin, were downregulated. Our results highlight that PFOS exposure may inhibit the synaptic plasticity of the hippocampus via glutamatergic synapse and the CREB/BDNF signaling pathway to cause depressive-like behaviors in male mice.

Perfluorooctane sulfonate promotes atherosclerosis by modulating M1 polarization of macrophages through the NF-κB pathway.

Perfluorooctane sulfonate (PFOS) is a widely used and distributed perfluorinated compounds and is reported to be harmful to cardiovascular health; however, the direct association between PFOS exposure and atherosclerosis and the underlying mechanisms remain unknown. Therefore, this study aimed to investigate the effects of PFOS exposure on the atherosclerosis progression and the underlying mechanisms. PFOS was administered through oral gavage to apolipoprotein E-deficient (ApoE-/-) mice for 12 weeks. PFOS exposure significantly increased pulse wave velocity (PWV) and intima-media thickness (IMT), increased aortic plaque burden and vulnerability, and elevated serum lipid and inflammatory cytokine levels. PFOS promoted aortic and RAW264.7 M1 macrophage polarization, which increased the secretion of nitric oxide synthase (iNOS) and pro-inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1ß [IL-1ß]), and suppressed M2 macrophage polarization, which decreased the expression of CD206, arginine I (Arg-1), and interleukin-10 (IL-10). Moreover, PFOS activated nuclear factor-kappa B (NF-κB) in the aorta and macrophages. BAY11-7082 was used to inhibit NF-κB-alleviated M1 macrophage polarization and the inflammatory response induced by PFOS in RAW264.7 macrophages. Our results are the first to reveal the acceleratory effect of PFOS on the atherosclerosis progression in ApoE-/- mice, which is associated with the NF-κB activation of macrophages to M1 polarization to induce inflammation.