Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation
Abstract
Previous studies have shown that ovarian estrogens are involved in the occurrence and pathology of Alzheimer's disease (AD) through regulation on hippocampal synaptic plasticity and spatial memory; however, the underlying mechanisms have not yet been elucidated at the genomic scale. In this study, we established the postmenopausal estrogen-deficient model by ovariectomy (OVX). Then, we used high-throughput Affymetrix Clariom transcriptomics and found 143 differentially expressed genes in the hippocampus of OVX mice with the absolute fold change ≥ 1.5 and P < 0.05. GO analysis showed that the highest enrichment was seen in long-term memory. Combined with the response to steroid hormone enrichment and GeneMANIA network prediction, the serum and glucocorticoid-regulated kinase 1 gene (Sgk1) was found to be the most potent candidate for ovarian estrogenic regulation. Sgk1 overexpression viral vectors (oSgk1) were then constructed and injected into the hippocampus of OVX mice. Morris water maze test revealed that the impaired spatial learning and memory induced by OVX was rescued by Sgk1 overexpression. Additionally, the altered expression of synaptic proteins and actin remodeling proteins and changes in CA1 spine density and synapse density induced by OVX were also significantly reversed by oSgk1. Moreover, the OVX-induced increase in Aβ-producing BACE1 and Aβ and the decrease in insulin degrading enzyme were significantly reversed by oSgk1. The above results show that multiple p…
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Overexpression of SGK1 in ovariectomized mice reverses reduction in synaptic protein expression, spine, and synapse density in the CA1 region.
“Overexpression of SGK1 in ovariectomized mice reverses the reduction in synaptic protein expression, spine, and synapse density in the CA1 region”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Liu et al., 2022
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- Authors
- Liu, M., Lian, B., Lan, Z., Sun, H., Zhao, Y., Sun, T., Meng, Z., Zhao, C., & Zhang, J.
- Affiliations
- Army Medical University (CN)
- Ningxia Medical University (CN)
- Chinese PLA General Hospital (CN)
- Corresponding author
- Zhao, Chengjun
- Zhang, Jiqiang
- Venue
- Neurochemical Research
- Published
- 2022-08-01
- Volume
- 47
- Issue
- 11
- Pages
- 3369-3384
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W4289277807
- Cited by
- 8
- References
- 66
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Ningxia Province (2020AAC03147)
- Postdoctoral Research Foundation of China (2019M653976)
- Chongqing Science and Technology Commission (cstc2019jcyj-msxmX0255))
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- SGK1, ovarian estrogen, estrogen deficiency, ovariectomy, Alzheimer's disease, hippocampus, spatial learning and memory, amyloid-beta deposition, BACE1, insulin-degrading enzyme, synaptic plasticity, postmenopausal estrogen deficiency, gene expression profiling
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Actins, Alzheimer Disease, Animals, Estrogens, Female, Hippocampus, Insulysin, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Maze Learning, Mice, Amyloid Precursor Protein Secretases, Transcriptome, Spatial Memory, Spatial Learning
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