Growing evidence indicates that postnatal immune activation (PIA) can adversely increase the lifetime risk for several neuropsychiatric disorders, including anxiety and depression, which involve the activation of glial cells and early neural developmental events. Several glia-targeted agents are required to protect neonates. Folic acid (FA), a clinical medication used during pregnancy, has been reported to have neuroprotective properties. However, the effects and mechanisms of FA in PIA-induced neonatal encephalitis and mood disorders remain unclear. Here, we investigated the roles of FA in a mouse model of PIA, and found that FA treatment improved depressive- and anxiety-like behaviors in adults, accompanied by a decrease in the number of activated microglia and astrocytes, as well as a reduction in the inflammatory response in the cortex and hippocampus of neonatal mice. Furthermore, we offer new evidence describing the functional differences in FA between microglia and astrocytes. Our data show that epigenetic regulation plays an essential role in FA-treated glial cells following PIA stimulation. In astrocytes, FA promoted the expression of IL-10 by decreasing the level of EZH2-mediated H3K27me3 at its promoter, whereas FA promoted the expression of IL-13 by reducing the promoter binding of H3K9me3 mediated by KDM4A in microglia. Importantly, FA specifically regulated the expression level of BDNF in astrocytes through H3K27me3. Overall, our data supported that FA may be an effective treatment for reducing mood disorders induced by PIA, and we also demonstrated significant functional differences in FA between the two cell types following PIA stimulation.

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Major depressive disorder takes at least 3 weeks for clinical anti-depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one-third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment-resistant depression patients. The rapid and strong anti-depressant-like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti-depressant-like effects. However, mechanisms about the rapid anti-depressant-like effects remain unclear. Elucidating the mechanisms of rapid anti-depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti-depressant-like effects based on the pre-clinical and clinical evidence, trying to provide new insight into future therapy.

Objective This study aimed to evaluate the expression level of long chain acyl-CoA synthase 1 (ACSL1) in clear cell renal cell carcinoma (ccRCC) tissue and explore its biological role in the progression of ccRCC.Methods Using Reversed Phase Protein Array (RPPA) sequencing technology, we identified ACSL1 as the target gene of interest. We then used the TCGA database to analyze the mRNA expression level of ACSL1 in ccRCC tissue and its clinical relevance. Immunohistochemistry and qRT-PCR were used to measure the expression level of ACSL1 in ccRCC tissue and investigate the correlation between ACSL1 expression level and clinicopathological characteristics and patient prognosis. CCK-8 technology and ferrostatin-1 were used to investigate the correlation between ACSL1 and ferroptosis in renal cancer cells. We also measured the content of malondialdehyde, glutathione, reactive oxygen species level, and degree of mitochondrial damage under electron microscopy to detect the effect of ACSL1 on ferroptosis of renal cancer cells. Additionally, we used RNA-Seq and Western blotting techniques to explore the potential mechanism of ACSL1 in renal cancer cells. Finally, we investigated the effect of ACSL1 on tumor growth using a xenotransplantation model.Results Our results showed that the expression level of ACSL1 in ccRCC tissue was significantly decreased and was correlated with clinical characteristics. The low expression level of ACSL1 was associated with poor patient prognosis. Overexpression of ACSL1 in renal cancer cells led to a significant decrease in GSH content, an improvement in the ability of lipid peroxidation, a significant increase in ROS level, significant shrinkage of intracellular mitochondria, and decreased expression of GPX4 and SLC7A11. RNA-Seq and KEGG enrichment analysis revealed that ACSL1 regulates ferroptosis in ccRCC through the HO-1/GPX4 axis. Western blotting confirmed that ACSL1 upregulated the expression of HO-1 and inhibited the expression of GPX4.Conclusion The expression of ACSL1 is low in human ccRCC tissue, and ACSL1 may be a potential target and prognostic marker for the treatment of ccRCC.