Serum- and glucocorticoid-inducible kinase 1 activity reduces dendritic spines in dorsal hippocampus
Open accessAbstract
The hippocampus has a well-known role in mediating learning and memory, and its function can be directly regulated by both stress and glucocorticoid receptor activation. Hippocampal contributions to learning are thought to be dependent on changes in the plasticity of synapses within specific subregions, and these functional changes are accompanied by morphological changes in the number and shape of dendritic spines, the physical correlates of these glutamatergic synapses. Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates dendritic spine morphology in the prefrontal cortex, and modulation of SGK1 expression in mouse hippocampus regulates learning. However, the role of SGK1 in dendritic spine morphology within the CA1 and dentate gyrus regions of the hippocampus are unknown. Thus, herpes simplex viral vectors expressing GFP and various SGK1 constructs, including wild type SGK1, a catalytically inactive version of SGK1 (K127Q), and a phospho-defective version of SGK1 (S78A), were infused into the hippocampus of adult mice and confocal fluorescent microscopy was used to visualize dendritic spines. We show that increasing expression of SGK1 in the dentate gyrus increased the total number of spines, driven primarily by an increase in mushroom spines, while decreasing SGK1 activity (K127Q) in the CA1 region increased the total number of dendritic spines, driven by a significant increase in mushroom and stubby spines. The differential effects of SGK1 in these regions may be mediated by the interactions of SGK1 with multiple pathways required for spine formation and stability. As the formation of mature synapses is a crucial component of learning and memory, this indicates that SGK1 is a potential target in the pathway underlying stress-associated changes in cognition and memory.
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LTP in the hippocampus is closely associated with phosphorylation of SGK1 at Ser422; dominant-negative SGK1 targeting Ser422 disrupts LTP with regional specificity.
“LTP in the hippocampus is closely associated with the phosphorylation of SGK1 at Ser422. Introducing a dominant-negative SGK1 targeting Ser422, disrupts LTP with regional specificity in the brain”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Steffke et al., 2020
The Introduction (page unavailable) reports increased SGK1 phosphorylation at Ser422 after protocols that induce hippocampal LTP, and says SGK1 inhibition impairs LTP expression but not induction. It does not report that a Ser422-targeting dominant-negative SGK1 disrupts LTP with regional specificity. The Results concern region-dependent dendritic spine changes, while the Discussion says regional effects on synaptic function and plasticity remain to be tested. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the dentate gyrus, increased SGK1 activity promotes maturation of dendritic spines, but the effect is opposite in the CA1 region.
“In the dentate gyrus, increased SGK1 activity promotes the maturation of dendritic spines. However, the effect is opposite in the CA1 region”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Steffke et al., 2020
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- Authors
- Steffke, E. E., Kirca, D., Mazei-Robison, M. S., & Robison, A. J.
- Affiliations
- Michigan State University (US)
- Corresponding author
- Robison, Alfred J.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 725
- Pages
- 134909
- ISSN
- 0304-3940 (ISSN-L)
- PMC
- PMC7232939
- OpenAlex
- W3012556591
- Cited by
- 10
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 2
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- SGK1, serum- and glucocorticoid-inducible kinase 1, dendritic spines, hippocampus, CA1, dentate gyrus, dendritic spine morphology, mushroom spines, stress, glucocorticoid receptor, synaptic plasticity, learning and memory
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Enzyme Activation, Genetic Vectors, Hippocampus, Male, Mice, Inbred C57BL, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Dendritic Spines, Green Fluorescent Proteins, Mice
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