Serum- and glucocorticoid-inducible kinase1 enhances contextual fear memory formation through down-regulation of the expression of Hes5
Abstract
Mitogen-activated protein kinase/extracellular signal-regulated kinase plays an important role in memory formation and directly phosphorylates serum- and glucocorticoid-inducible kinase1 (SGK1) at Ser78. In this study, we examined the role and mechanism of SGK1 Ser78 activation involved in contextual fear memory formation in rats. Results revealed that SGK1 Ser78 phosphorylation was increased 30 min, 1 h and 3 h after training. Transient transfection of the dominant negative mutant of sgk, sgkS78A, to hippocampal neurons impaired, whereas transfection of the constitutively active sgk, sgkS78D, enhanced fear retention. Microarray analysis identified 14 genes that showed more than threefold alteration in their gene expression in sgkS78A-transfected animals 6 h after training. One of them is Hairy and Enhancer of split 5 (Hes5). The expression level of Hes5 is approximately 4.4-fold higher in sgkS78A-transfected animals. Further analyses revealed that Hes5 level is markedly decreased after training in control animals, but sgkS78A markedly increased Hes5 level after training. RNA interference experiment showed that shHes5 dose-dependently enhanced fear retention, whereas over-expression of Hes5 impaired fear retention. Moreover, shHes5 at a lower concentration completely blocked the memory-impairing effect of sgkS78A. These results together suggest that Hes5 negatively regulates contextual fear memory formation and SGK activation down-regulates Hes5 expression to enhance fear ret…
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Transfection of inactive SGK1 to hippocampal neurons impairs fear retention.
“Transfection of inactive SGK1 to hippocampal neurons further impaired, whereas transfection of constitutively active SGK1 enhanced, fear retention (Lee et al. 2007).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lee et al. 2007
SGK1 downregulation of Hes5 results in enhanced fear retention.
“SGK1 downregulates Hairy and Enhancer of split 5 (Hes5) resulting in enhanced fear retention, whereas over-expression of Hes5 negatively regulates contextual fear memory formation (Lee et al. 2007).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lee et al. 2007
Transfection of constitutively active SGK1 to hippocampal neurons enhances fear retention.
“Transfection of inactive SGK1 to hippocampal neurons further impaired, whereas transfection of constitutively active SGK1 enhanced, fear retention (Lee et al. 2007).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lee et al. 2007
SGK1 downregulates Hairy and Enhancer of split 5 (Hes5).
“SGK1 downregulates Hairy and Enhancer of split 5 (Hes5) resulting in enhanced fear retention, whereas over-expression of Hes5 negatively regulates contextual fear memory formation (Lee et al. 2007).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lee et al. 2007
Over-expression of Hes5 negatively regulates contextual fear memory formation.
“SGK1 downregulates Hairy and Enhancer of split 5 (Hes5) resulting in enhanced fear retention, whereas over-expression of Hes5 negatively regulates contextual fear memory formation (Lee et al. 2007).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lee et al. 2007
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Fanselow, M. S. (1986) · Learning and Motivation · doi:10.1016/0023-9690(86)90018-4 · Cited by 326 · see citing works
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Significance of SGK1 in the regulation of neuronal function
Lang, F., Strutz-Seebohm, N., Seebohm, G., & Lang, U. E. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.190926 · Cited by 170 · see citing works
Serum- and glucocorticoid-inducible kinase 1 activity reduces dendritic spines in dorsal hippocampus
Steffke, E. E., Kirca, D., Mazei-Robison, M. S., & Robison, A. J. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134909 · Cited by 10 · see citing works
Behavioral effects of SGK1 knockout in VTA and dopamine neurons
Doyle, M. A., Stark, A. R., Fejes-Tóth, G., Náray-Fejes-Tóth, A., & Mazei-Robison, M. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-71681-9 · Cited by 9 · see citing works
Liu, M., Lian, B., Lan, Z., Sun, H., Zhao, Y., Sun, T., Meng, Z., Zhao, C., & Zhang, J. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03690-1 · Cited by 8 · see citing works
- Authors
- Lee, C. T., Ma, Y. L., & Lee, E. H. Y.
- Affiliations
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-11
- Volume
- 100
- Issue
- 6
- Pages
- 1531-1542
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2086979442
- Cited by
- 32
- References
- 1
- Citations by year
- 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 5
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- SGK1, serum- and glucocorticoid-inducible kinase 1, Hes5, contextual fear memory, ERK signaling, hippocampal neurons, gene expression regulation, dominant-negative mutant, shRNA knockdown
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Acoustic Stimulation, Animals, Behavior, Animal, Conditioning, Classical, Fear, Male, Memory, Motor Activity, Repressor Proteins, RNA, Messenger, Serine, Time Factors, Down-Regulation, PC12 Cells, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Gene Transfer Techniques, Reverse Transcriptase Polymerase Chain Reaction, Animals, Genetically Modified, RNA Interference, Green Fluorescent Proteins, Rats, Basic Helix-Loop-Helix Proteins
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