Effects of Novelty Stress on Hippocampal Gene Expression, Corticosterone and Motor Activity in Mice
Abstract
Exposure to novelty, a mild psychological stressor, induces neuronal activations in the hippocampus of rodents, which may play an important role in the adaptation to stress. We examined the changes in three parameters, i.e., gene expression in the hippocampus using a RT-PCR method, corticosterone and motor activity, in mice exposed to a new environment for 120min. A sharp and short-lasting increase in the gene expression of a set of stress-related genes previously reported, e.g., Fos and Nr4a1, was observed during the stress, with a similar pattern of changes in corticosterone. The motor activity gradually decreased during the novelty stress, indicating a process of adaptation to the new environment. In addition, in order to minimize the effects of elevated adrenal hormones by the stress, we carried out experiments on adrenalectomized (ADX) mice. However, the adrenalectomy produced minimal changes in the pattern and the magnitude of the gene response after the stress, while the motor activity showed a relatively slower pattern of adaptation in the ADX mice. Hence, the present study suggests that there was a coordinated adaptation process to the new environment in mice, and that the transcriptional response was mediated by neuronal networks rather than by adrenal hormones.
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Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).
“Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).”
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [109]
Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience.
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [109]
Studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation.
“Similarly, studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation [17,22,41,109].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [109]
Cites
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · cited 2× · see citing works
“Many studies indicate that the hippocampus is one of the most important brain regions subject to the coordinate stress-response system (Joëls and Baram, 2009; De Kloet et al., 2005; McEwen, 2007; Oitzl et al., 2010).”
BackgroundStress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · see citing works
Housekeeping genes as internal standards: use and limits
Thellin, O., Zorzi, W., Lakaye, B., Borman, B. D., Coumans, B., Hennen, G. P., Grisar, T. M., Igout, A., & Heinen, E. (1999) · Journal of Biotechnology · doi:10.1016/s0168-1656(99)00163-7 · Cited by 1,534 · see citing works
Joëls, M., & Baram, T. Z. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2632 · Cited by 1,521 · see citing works
Pattern and time course of immediate early gene expression in rat brain following acute stress
Cullinan, W. E., Herman, J. P., Battaglia, D. F., Akil, H., & Watson, S. J. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00355-9 · Cited by 1,056 · see citing works
Stressor specificity of central neuroendocrine responses: implications for stress-related disorders
Pacák, K., & Palkovits, M. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.4.0436 · Cited by 926 · see citing works
Contribution of human hippocampal region to novelty detection
Knight, R. T. (1996) · Nature · doi:10.1038/383256a0 · Cited by 834 · see citing works
CCN proteins: multifunctional signalling regulators
Perbal, B. (2004) · The Lancet · doi:10.1016/s0140-6736(03)15172-0 · Cited by 704 · see citing works
Corticosteroids in relation to fear, anxiety and psychopathology
Korte, S. M. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00002-1 · Cited by 607 · see citing works
Selective Loss of Hippocampal Granule Cells in the Mature Rat Brain After Adrenalectomy
Sloviter, R. S., Valiquette, G., Abrams, G., Ronk, E. C., Sollas, A. L., Paul, L. A., & Neubort, S. (1989) · Science · doi:10.1126/science.2911756 · Cited by 526 · see citing works
Rapid Glucocorticoid Signaling via Membrane-Associated Receptors
Tasker, J. G., Di, S., & Malcher‐Lopes, R. (2006) · Endocrinology · doi:10.1210/en.2006-0981 · Cited by 401 · see citing works
Brain development under stress: Hypotheses of glucocorticoid actions revisited
Oitzl, M. S., Champagne, D. L., van der Veen, R., & de Kloet, E. R. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.07.006 · Cited by 358 · see citing works
Distribution of spatial and nonspatial information in dorsal hippocampus
Hampson, R. E., Simeral, J. D., & Deadwyler, S. A. (1999) · Nature · doi:10.1038/45154 · Cited by 303 · see citing works
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem
Béguin, P., Nagashima, K., Gonoi, T., Shibasaki, T., Takahashi, K., Kashima, Y., Ozaki, N., Geering, K., Iwanaga, T., & Seino, S. (2001) · Nature · doi:10.1038/35079621 · Cited by 291 · see citing works
Regulation of hippocampal H3 histone methylation by acute and chronic stress
Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911143106 · Cited by 290 · see citing works
The role of hippocampal subregions in detecting spatial novelty
Lee, I., Hunsaker, M. R., & Kesner, R. P. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.1.145 · Cited by 270 · see citing works
Giovannini, M. G., Rakovska, A., Benton, R. S., Pazzagli, M., Bianchi, L., & Pepeu, G. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00266-4 · Cited by 267 · see citing works
Stress-induced expression of immediate early genes in the brain and peripheral organs of the rat
Senba, E., & Ueyama, T. (1997) · Neuroscience Research · doi:10.1016/s0168-0102(97)00095-3 · Cited by 249 · see citing works
Datson, N. A., van der Perk, J., de Kloet, E. R., & Vreugdenhil, E. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01685.x · Cited by 230 · see citing works
Genomic and non-genomic effects of glucocorticoids on aggressive behavior in male rats
Mikics, É., Kruk, M. R., & Haller, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00090-8 · Cited by 218 · see citing works
Tirone, F. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1062 · Cited by 213 · see citing works
Iacopetti, P., Michelini, M., Stuckmann, I., Oback, B. J., Aaku‐Saraste, E., & Huttner, W. Β. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4639 · Cited by 207 · see citing works
Novelty‐related Rapid Locomotor Effects of Corticosterone in Rats
Sandi, C., Venero, C., & Guaza, C. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01264.x · Cited by 207 · see citing works
Imaki, T., Shibasaki, T., Hotta, M., & Demura, H. (1993) · Brain Research · doi:10.1016/0006-8993(93)90199-w · Cited by 197 · see citing works
Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins
Chaqour, B., & Goppelt‐Struebe, M. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05360.x · Cited by 189 · see citing works
Environmental novelty is signaled by reduction of the hippocampal theta frequency
Jeewajee, A., Lever, C., Burton, S., O'Keefe, J. M., & Burgess, N. (2007) · Hippocampus · doi:10.1002/hipo.20394 · Cited by 189 · see citing works
Hippocampal corticotropin releasing hormone: pre- and postsynaptic location and release by stress
Chen, Y., Brunson, K. L., Adelmann, G., Bender, R. A., Frotscher, M., & Baram, T. Z. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.036 · Cited by 179 · see citing works
VanElzakker, M. B., Fevurly, R. D., Breindel, T., & Spencer, R. L. (2008) · Learning & Memory · doi:10.1101/lm.1196508 · Cited by 179 · see citing works
Gem: an Induced, Immediate Early Protein Belonging to the Ras Family
Maguire, J. E., Santoro, T. J., Jensen, P. N., Siebenlist, U. K., Yewdell, J. W., & Kelly, K. (1994) · Science · doi:10.1126/science.7912851 · Cited by 178 · see citing works
Mikics, É., Barsy, B., Barsvári, B., & Haller, J. (2005) · Hormones and Behavior · doi:10.1016/j.yhbeh.2005.02.002 · Cited by 131 · see citing works
Hansson, A. C., Cintra, A., Belluardo, N., Sommer, W. H., Bhatnagar, M., Bäder, M., Ganten, D., & Fuxé, K. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00185.x · Cited by 124 · see citing works
Chandramohan, Y., Droste, S. K., & Reul, J. M. H. M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04396.x · Cited by 117 · see citing works
Lim, I. K. (2006) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-006-0080-1 · Cited by 106 · see citing works
de Groote, L., & Linthorst, A. C. E. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.06.030 · Cited by 100 · see citing works
Nur77 and retinoid X receptors: crucial factors in dopamine-related neuroadaptation
Lévesque, D., & Rouillard, C. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.11.006 · Cited by 98 · see citing works
CRF signaling: molecular specificity for drug targeting in the CNS
ARZT, E. S., & Holsboer, F. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.08.007 · Cited by 96 · see citing works
Castelló, R., Estellés, A., Vázquez, C., et al. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.8.1288 · Cited by 85 · see citing works
Effects of novelty, pain and stress on hippocampal extracellular acetylcholine levels in male rats
Aloisi, A. M., Casamenti, F., Scali, C., Pepeu, G., & Carli, G. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01304-2 · Cited by 83 · see citing works
Riedemann, T., Patchev, A. V., Cho, K., & Almeida, O. F. X. (2010) · Molecular Brain · doi:10.1186/1756-6606-3-2 · Cited by 62 · see citing works
Pace, T. W. W., Gaylord, R. I., Topczewski, F., Girotti, M., Rubin, B., & Spencer, R. L. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04354.x · Cited by 57 · see citing works
Induction of NGFI-B mRNA following contextual fear conditioning and its blockade by diazepam
Malkani, S., & Rosen, J. B. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00130-3 · Cited by 44 · see citing works
Accessory adrenal cortical nodules in the mouse
Hummel, K. P. (1958) · The Anatomical Record · doi:10.1002/ar.1091320305 · Cited by 44 · see citing works
Response of extracelluar zinc in the ventral hippocampus against novelty stress
Takeda, A., Sakurada, N., Kanno, S., et al. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04092.x · Cited by 35 · see citing works
Kaneko, Y., Kashiwa, A., Ito, T., Ishii, S., Umino, A., & Nishikawa, T. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301111 · Cited by 27 · see citing works
Self-citationSchiltz, C. A., Kelley, A. E., & Landry, C. F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.002 · Cited by 18 · see citing works
Effects of FG7142 and immobilization stress on the gene expression in the neocortex of mice
Kurumaji, A., Ito, T., Ishii, S., & Nishikawa, T. (2008) · Neuroscience Research · doi:10.1016/j.neures.2008.08.001 · Cited by 14 · see citing works
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- Authors
- Kurumaji, A., Umino, M., & Nishikawa, T.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Kurumaji, Akeo
- ORCID
- Nishikawa, Toru
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 71
- Issue
- 2
- Pages
- 161-167
- ISSN
- 0168-0102 (ISSN-L)
- OpenAlex
- W2054138345
- Cited by
- 18
- References
- 46
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- novelty stress, hippocampus, gene expression, corticosterone, motor activity, FOS, Nur77, adrenalectomy, stress adaptation, adrenal hormones
- MeSH terms
- Adaptation, Physiological, Adrenalectomy, Animals, Corticosterone, Exploratory Behavior, Gene Expression Regulation, Hippocampus, Male, Mice, Inbred C57BL, Motor Activity, Stress, Psychological, Mice
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