Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation

Liu, Mengying; Lian, Biyao; Zhen, Linlin; Sun, Huan; Zhao, Yangang; Sun, Tao; Meng, Ziqi; Zhao, Caidan; Zhang, Jiqiang

doi:10.1007/s11064-022-03690-1

Cited by 5 publications

(2 citation statements)

References 65 publications

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“…It was known that estrogen promotes placenta trophoblast viability and invasion by activating SGK1, 83 and overexpression of Sgk1 could rescue mouse spatial learning and memory impairments induced by estrogen deficiency. 84 In the present study, we demonstrated that coexposure to HMS and PNSs could up-regulate SGK1 through

activation, leading to the promotion of MCF-7 cell proliferation. To the best of our knowledge, this is the first report linking SGK1 to exogenous pollutant-induced estrogenic effects.…”

Section: Discussionsupporting

confidence: 53%

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish

Ye,

Li,

Xian

et al. 2024

Environ Health Perspect

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Background: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. Objectives: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo . Methods: We assessed the impact of polystyrene nanospheres (PNSs; , ) on HMS-induced MCF-7 cell proliferation (HMS: , equivalent to ) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS ( ) with or without PNSs ( , ) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus–pituitary–gonad–liver (HPGL) axis. Results: Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor ( ESR1 ) and the mRNAs of target genes ( pS2 , AREG , and PGR ), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of SGK1 and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes ( cyp17a2 , hsd17 1 , esr2b , vtg1 , and vtg2 ), and resulted in higher ( ) release in females. Conversely, males showed lower testosterone, , and gene expressions of cyp11a1 , cyp11a2 , cyp17a1 , cyp17a2 , and hsd17 1 . Discussion: PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696

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activation, leading to the promotion of MCF-7 cell proliferation. To the best of our knowledge, this is the first report linking SGK1 to exogenous pollutant-induced estrogenic effects.…”

Section: Discussionsupporting

confidence: 53%

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish

Ye,

Li,

Xian

et al. 2024

Environ Health Perspect

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“…SGK1 is engaged in various neurodegenerative pathways related to, e.g., apoptosis, autophagy, neuroinflammation, and ion channel regulation. Interestingly, hippocampal overexpression of Sgk1 improved spatial memory, reduced the devastating impact of Aβ accumulation and rescued actin cytoskeleton polymerization in middle-aged APP/PS1 mice [ 164 , 165 ]. It has been speculated that Sgk1 could exert a protective role against oxidative stress and play an antiapoptotic role [ 166 ].…”

Section: Discussionmentioning

confidence: 99%

Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer’s disease mice

Papazoglou,

Henseler,

Weickhardt

et al. 2024

PLoS ONE

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A variety of Alzheimer’s disease (AD) mouse models has been established and characterized within the last decades. To get an integrative view of the sophisticated etiopathogenesis of AD, whole genome transcriptome studies turned out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex and hippocampus of age-matched, eight months old male and female APP/PS1 AD mice and control animals to perform sex- and brain region specific analysis of transcriptome profiles. The results of our studies reveal novel, detailed insight into differentially expressed signature genes and related fold changes in the individual APP/PS1 subgroups. Gene ontology and Venn analysis unmasked that intersectional, upregulated genes were predominantly involved in, e.g., activation of microglial, astrocytic and neutrophilic cells, innate immune response/immune effector response, neuroinflammation, phagosome/proteasome activation, and synaptic transmission. The number of (intersectional) downregulated genes was substantially less in the different subgroups and related GO categories included, e.g., the synaptic vesicle docking/fusion machinery, synaptic transmission, rRNA processing, ubiquitination, proteasome degradation, histone modification and cellular senescence. Importantly, this is the first study to systematically unravel sex- and brain region-specific transcriptome fingerprints/signature genes in APP/PS1 mice. The latter will be of central relevance in future preclinical and clinical AD related studies, biomarker characterization and personalized medicinal approaches.

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Integrating analysis of mRNA expression profiles indicates Sgk1 as a key mediator in muscle-brain crosstalk during resistance exercise

Liu,

Ye,

Dai

et al. 2024

Biochemical and Biophysical Research Communications

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Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation

Cited by 5 publications

References 65 publications

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish

Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer’s disease mice

Integrating analysis of mRNA expression profiles indicates Sgk1 as a key mediator in muscle-brain crosstalk during resistance exercise

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