Sex-specific role for microglial CST7 in Alzheimer’s disease

Balevičiūtė, Austėja; Keane, Lily

doi:10.1038/s41577-022-00830-0

Cited by 6 publications

(2 citation statements)

References 1 publication

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“…Moreover, we also demonstrated that the expression level of CST7 was significantly upregulated in the hippocampus of APP/PS1 mice, while that was suppressed with TSA. These data are consistent with previous research shown that CST7 is upregulated in AD ( Rasmussen et al, 2022 ; Baleviciute and Keane, 2023 ). We further investigated this in vitro and showed that TSA reduced LPS-induced CST7 expression in BV2 cells.…”

Section: Introductionsupporting

confidence: 94%

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice

Su,

Ren,

Liu

et al. 2024

Front. Pharmacol.

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Background:Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer’s disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly.Methods:In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia.Results:The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells.Conclusion:Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

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Section: Introductionsupporting

confidence: 94%

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice

Su,

Ren,

Liu

et al. 2024

Front. Pharmacol.

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“…Coinciding with the cathepsin family of genes in microglia, Cst7 is also implicated in the neuroinflammation that occurs with Alzheimer’s and prion disease [ 56 , 57 ]. Expression of Cst7 is notably expressed in microglia of AD pathology and has recently been considered a sex-dependent indicator for AD [ 58 , 59 ]. Cst7 expressing microglia tend to surround Aβ in the brain and increase inflammation [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer’s disease by activated protein C

Fatmi,

Wang,

Slotabec

et al. 2024

Aging

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Single-Cell RNA sequencing reveals changes in cell population in Alzheimer’s disease (AD) model 5xFAD (5x Familial AD mutation) versus wild type (WT) mice. The returned sequencing data was processed through the 10x Genomics CellRanger platform to perform alignment and form corresponding matrix to perform bioinformatic analysis. Alterations in glial cells occurred in 5xFAD versus WT, especially increases in microglia proliferation were profound in 5xFAD. Differential expression testing of glial cells in 5xFAD versus WT revealed gene regulation. Globally, the critical genes implicated in AD progression are upregulated such as Apoe , Ctsb , Trem2 , and Tyrobp . Using this differential expression data, GO term enrichment was completed to observe possible biological processes impacted by AD progression. Utilizing anti-inflammatory and cyto-protective recombinant Activated Protein C (APC), we uncover inflammatory processes to be downregulated by APC treatment in addition to recuperation of nervous system processes. Moreover, animal studies demonstrated that administration of recombinant APC significantly attenuated Aβ burden and improved cognitive function of 5xFAD mice. The downregulation of highly expressed AD biomarkers in 5xFAD could provide insight into the mechanisms by which APC administration benefits AD.

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