Possible role of arginase 1 positive microglia on depressive/anxiety-like behaviors in atopic dermatitis mouse model

Yang, Bohyun; Ryu, Jae Sang; Rim, Chan; Shin, Jung U; Kwon, Min Soo

doi:10.1007/s12272-022-01369-3

Cited by 9 publications

(11 citation statements)

References 59 publications

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“…Increased serum Gc levels caused by a chronically activated HPA axis may lead to GR insensitivity, which manifests in the form of decreased GR expression [69]. A decrease in ARG-1 positive microglia in the HPC is reportedly associated with depressive-like behavior [29], while an imbalance in the hypothalamic-pituitary-adrenal axis (HPA axis) was also found to be related to depressive-like behavior [29,70]. These data provide mounting evidence supporting the previous contention that cellular and molecular mechanisms may underly depression-like behavior.…”

Section: Discussionmentioning

confidence: 99%

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Microglia involvement in the schizophrenia occurrence in male offspring with maternal dexamethasone exposure

Rim

Park

You

et al. 2022

Preprint

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Background: Fetal microglia are particularly sensitive cells to the changes in utero environment and show sex-biased differences in shape and function. Maternal stress hormone induction can affect fetal microglial functions including alterations in synaptic pruning and cytokine secretion. It may contribute to psychiatric outcomes in offspring such as schizophrenia and depression. Methods: We administered a 50 µg/kg dexamethasone (DEX) to dams subcutaneously from gestational days 16 to 18. To characterize behaviors of maternal DEX exposed offspring, we assessed depressive-like and schizophrenia-relevant behaviors among 5 week old (adolescence), 10 week old (adult), and orchiectomized group respectively. Using quantitative real-time polymerase chain reaction, western blotting, and rapid Golgi staining, microglial morphology and synaptic pruning were assessed. Results: Prenatal exposure to dexamethasone (PN-DEX) induced SCZ-relevant behavior in male mice and depressive-like behavior in female mice. SCZ-relevant behavioral patterns were induced in 10 week old (10 W) male mice but not in 5 week old (5 W) male mice. Microglia in the medial prefrontal cortex (mPFC) and the striatum (STR) of 10 W males prenatally treated with dexamethasone (10 W PN-DEX-M) showed hyper-ramified morphology and dramatically reduced spine density in mPFC. Immunofluorescence studies indicated that microglia in the mPFC of the 10 W PN-DEX-M group interacted with pre-synaptic Bassoon and post-synaptic density 95 (PSD95) puncta. PN-DEX-M also showed significantly changed dopamine system proteins. A testosterone surge was not observed in parallel to SCZ-relevant behavior in 10 W PN-DEX-M. Furthermore, females prenatally treated with dexamethasone (PN-DEX-F) displayed depressive-like behavior, in addition to HPA axis activation and inflammatory microglial phenotypes in their hippocampus (HPC).Conclusions: Our study demonstrated that maternal DEX exposure induces sex-biased abnormal behavior as well as SCZ-relevant behavior in male offspring, and depressive-like behaviors in female offspring. We propose that altered microglial function, such as increased synaptic pruning, may be involved in the occurrence of SCZ-relevant behavior in PN-DEX-M and sex-biased abnormal behavior in the PN-DEX model.

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Section: Discussionmentioning

confidence: 99%

“…Microglial morphology was analyzed according to a previously described method [29]. In brief, z-stacked confocal images (1 µm slices) were converted to maximum intensity projection images using ImageJ.…”

Section: Skeletal and Sholl Analysismentioning

confidence: 99%

Microglia involvement in the schizophrenia occurrence in male offspring with maternal dexamethasone exposure

Rim

Park

You

et al. 2022

Preprint

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“…Previous studies had shown that pathways include neutrophil degranulation [74], immune system [75], extracellular matrix organization [76], toll-like receptor cascades [77], cytokine signaling in immune system [78], metabolism of RNA [79] and gene expression [80] were involved in the progression of CF. NTRK3 [81], MMP9 [82], IGF2 [83], SOCS3 [84], IGFBP2 [85], SLC1A3 [86], NOS1AP [87], HP (haptoglobin) [88], TLR5 [89], ARG1 [90], NRG1 [91], RGS5 [92], LCN2 [93], TSPO (translocator protein) [94], PLAU (plasminogen activator, urokinase) [95], MME (membrane metalloendopeptidase) [96], BST1 [97], NR6A1 [98], TLR4 [99], NRN1 [100], ABCA13 [101], CTSD (cathepsin D) [102], NCAM1 [103], SIGMAR1 [104], CNR2 [105], CCR4 [106], ABCB1 [107], TIMELESS (timeless circadian regulator) [108], IRF8 [109], TXNIP (thioredoxin interacting protein) [110], SUV39H1 [111], CRY1 [112], CRY2 [113], PDCD4 [114] and MGAT5 [115] played an important role in depression and anxiety. Accumulating evidence has demonstrated that MMP9 [116], S100A12 [117], HP (haptoglobin) [118], TLR5 [119], NRG1 [120], PLAU (plasminogen activator, urokinase) [121], SLC11A1 [122], AQP9 [123], CHIT1 [124], TLR4 [125], SLC26A8 [126], CTSD (cathepsin D) [127], SERPINB1 [128], FASLG (Fas ligand) [129], SLC4A4 [130], AQP3 [131] and IRF8 [132] appears to be constitutively associated with CF .…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Underlying Mechanisms in Cystic Fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Cystic fibrosis (CF) is one of the inherited autosomal recessive disorders with very complicated pathogenesis. Identifying the molecular signatures and specific biomarkers of CF might provide novel clues for CF and and CF associated complications prognosis and targeted therapy. Based on the nexgeneration sequencing (NGS) dataset GSE136371 downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) between CF samples and normal controls were identified by using DESeq2 bioconductor package of R software. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Then protein-protein interaction (PPI) network of these DEGs was visualized by Cytoscape with IMEx interactome database. The most significant module from the PPI network was selected for GO and pathway enrichment analysis. Subsequently, a miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Finally, receiver operating characteristic curve (ROC) analysis was established to validate these hub genes. Total of 917 DEGs were identified between CF and normal control samples in GSE136371 dataset, including 479 up regulated and 438 down regulated genes. The most enriched DEGs in GO and pathway enrichment analysis were mainly associated with response to stimulus, regulation of cellular process, Neutrophil degranulation and rRNA processing. PPI network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network predicted ten hub genes (FN1, UBE2D1, SRPK1, MAPK14, CEBPB, HSP90AB1, HSPA8, XRCC6, NCL and PARP1). In conclusion, the DEGs, relative pathways and hub genes identified in the present study might aid in understanding of the molecular mechanisms underlying CF and CF associated complications progression and provide potential molecular targets and biomarkers for CF and CF associated complications.

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“…50 µg/kg DEX (Sigma, D1756) and physiological saline as control were injected subcutaneously into pregnant mice once a day for 3 days (gestational day: GD16 to 18) to recapitulate elevation of stress hormones during the antenatal period (Rim et al, 2022).…”

Section: Dexamethasone Treatment In Pregnant Micementioning

confidence: 99%

“…Although many studies have focused on neurons in PPD (Maguire and Mody, 2008;Haim et al, 2014), a few studies have focused on glial cells. Previously, we reported that dexamethasone (DEX) administration during pregnancy induced schizophrenia-relevant behaviors in male offspring and depressive-and anxiety-like behaviors in female offspring (Rim et al, 2022). In this model, we examined depressive-and anxiety-like behaviors in postpartum dams following DEX administration during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression

Kim

You

Sung

et al. 2023

Front. Cell. Neurosci.

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Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16–18) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks). DEX-dam showed anxiety-like behaviors in open-field test (OFT) and light–dark test (LD). In addition, DEX-dam exhibited depressive-like behaviors with the increased immobility time in forced swimming test (TST). Molecular analysis confirmed that microglia, rather than neurons, astrocytes, and oligodendrocytes, are involved in anxiety-/depressive-like behaviors. Notably, P2ry12, homeostatic gene, and purinoceptor, along with hyper-ramified form, were reduced in the hippocampus of DEX-dam. In addition, we found that IL-10 mRNA was reduced in lymph nodes without alteration of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Interestingly, anxiety-/depressive-like behaviors of DEX-dam were restored with the normalization of P2ry12 and IL-10 after 10 weeks postpartum without antidepressants. Our results propose that stress hormone elevation during pregnancy might be associated with PPD via microglial P2RY12 and peripheral IL-10.

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Possible role of arginase 1 positive microglia on depressive/anxiety-like behaviors in atopic dermatitis mouse model

Cited by 9 publications

References 59 publications

Microglia involvement in the schizophrenia occurrence in male offspring with maternal dexamethasone exposure

Microglia involvement in the schizophrenia occurrence in male offspring with maternal dexamethasone exposure

Identification of Key Genes and Underlying Mechanisms in Cystic Fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression

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