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Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors
Open accessAbstract
Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF 1 ) located on pyramidal cell dendrites. Additionally, chronic CRF 1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH expression is augmented in hippocampus of middle-aged CES rats, and then tested whether the morphological defects and poor memory performance in these animals involve excessive activation of CRF 1 receptors. Central or peripheral administration of a CRF 1 blocker following the stress period improved memory performance of CES rats in novel-object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH–CRF 1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF 1 occupancy post hoc normalized hippocampal function during middle age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress.
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“potential threats activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to enhanced expression of corticotropin releasing hormone (CRH) in the hippocampus and damage to hippocampal neurons (Brunson et al., 2001; Ivy et al., 2010).”
From Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience (2014) · cites this paper as Ivy et al., 2010
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Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
Effects of stress throughout the lifespan on the brain, behaviour and cognition
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2639 · Cited by 6,256
STRESS AND HIPPOCAMPAL PLASTICITY
McEwen, B. S. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.105 · Cited by 2,087
The link between childhood trauma and depression: insights from HPA axis studies in humans
Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.03.008 · Cited by 1,704
Joëls, M., & Baram, T. Z. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2632 · Cited by 1,521
Self-citationDendritic spine changes associated with hippocampal long-term synaptic plasticity
Engert, F., & Bonhoeffer, T. (1999) · Nature · doi:10.1038/19978 · Cited by 1,412
Recognition memory and the medial temporal lobe: a new perspective
Squire, L. R., Wixted, J. T., & Clark, R. E. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2154 · Cited by 1,059
Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses
Zhou, Q., Homma, K. J., & Poo, M.-M. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.011 · Cited by 1,025
Spatial memory, recognition memory, and the hippocampus
Broadbent, N. J., Squire, L. R., & Clark, R. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406344101 · Cited by 985
Cognitive Recovery in Socially Deprived Young Children: The Bucharest Early Intervention Project
Nelson, C. A., Zeanah, C. H., Fox, N. A., Marshall, P. J., Smyke, A. T., & Guthrie, D. (2007) · Science · doi:10.1126/science.1143921 · Cited by 951
LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite
Toni, N., Buchs, P.-A., Nikonenko, I., Bron, C. R., & Muller, D. (1999) · Nature · doi:10.1038/46574 · Cited by 949
Bidirectional Activity-Dependent Morphological Plasticity in Hippocampal Neurons
Nägerl, U. V., Eberhorn, N., Cambridge, S. B., & Bonhoeffer, T. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.016 · Cited by 602
Winters, B. D., Forwood, S., Cowell, R. A., Saksida, L. M., & Bussey, T. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1346-04.2004 · Cited by 588
Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Comparison of stressors
Magarin˜os, A. M., & McEwen, B. S. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00256-i · Cited by 571
Object recognition memory and the rodent hippocampus
Broadbent, N. J., Gaskin, S., Squire, L. R., & Clark, R. E. (2010) · Learning & Memory · doi:10.1101/lm.1650110 · Cited by 568
A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress
Rice, C. J., Sandman, C. A., Lenjavi, M. R., & Baram, T. Z. (2008) · Endocrinology · doi:10.1210/en.2008-0633 · Cited by 521
Self-citationDendritic spines and long-term plasticity
Segal, M. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1649 · Cited by 489
Mechanisms of late-onset cognitive decline after early-life stress
Brunson, K. L., Kramár, E., Lin, B., Chen, Y., Colgin, L. L., Yanagihara, T. K., Lynch, G., & Baram, T. Z. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2281-05.2005 · Cited by 479
Self-citationLee, Y., & Davis, M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-16-06434.1997 · Cited by 457
The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine
Harvey, C. D., Yasuda, R., Zhong, H., & Svoboda, K. (2008) · Science · doi:10.1126/science.1159675 · Cited by 434
Ivy, A. S., Brunson, K. L., Sandman, C., & Baram, T. Z. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.019 · Cited by 407
Self-citationAvishai‐Eliner, S. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02241-5 · Cited by 405
Corticosteroid hormones in the central stress response: Quick-and-slow
de Kloet, E. R., Karst, H., & Joëls, M. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.10.002 · Cited by 391
Childhood socioeconomic position and cognitive function in adulthood
Kaplan, G. A., Turrell, G., Lynch, J. W., Everson‐Rose, S. A., Helkala, E., & Salonen, J. T. (2001) · International Journal of Epidemiology · doi:10.1093/ije/30.2.256 · Cited by 347
Effects of Chronic Stress on Structure and Cell Function in Rat Hippocampus and Hypothalamus
Joëls, M., Karst, H., Alfarez, D., Heine, V. M., Qin, Y., Riel, E. V., Verkuyl, M., Lucassen, P. J., & Krugers, H. J. (2004) · Stress · doi:10.1080/10253890500070005 · Cited by 330
Effects of chronic stress on hippocampal long‐term potentiation
Pavlides, C., Nivón, L. G., & McEwen, B. S. (2002) · Hippocampus · doi:10.1002/hipo.1116 · Cited by 316
Changes in Synaptic Morphology Accompany Actin Signaling during LTP
Chen, L. Y., Rex, C. S., Casale, M. S., Gall, C. M., & Lynch, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0164-07.2007 · Cited by 296
Self-citationBale, T. L., Picetti, R., Contarino, A., Koob, G. F., Vale, W., & Lee, K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00193.2002 · Cited by 293
Rainnie, D. G., Bergeron, R., Sajdyk, T. J., Patil, M. M., Gehlert, D. R., & Shekhar, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5740-03.2004 · Cited by 293
Integration of biochemical signalling in spines
Kennedy, M. B., Beale, H. C., Carlisle, H. J., & Washburn, L. R. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1685 · Cited by 286
Chen, Y., Dubé, C. M., Rice, C. J., & Baram, T. Z. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0225-08.2008 · Cited by 276
Self-citationChen, Y., Rex, C. S., Rice, C. J., Dubé, C. M., Gall, C. M., Lynch, G., & Baram, T. Z. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003825107 · Cited by 256
Self-citationBredy, T. W., Humpartzoomian, R., Cain, D. P., & Meaney, M. J. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00918-1 · Cited by 253
Brunson, K. L., Eghbal-Ahmadi, M., Bender, R., Chen, Y., & Baram, T. Z. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151224898 · Cited by 236
Self-citationBlank, T., Nijholt, I. M., Eckart, K., & Spiess, J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03788.2002 · Cited by 235
Abnormal corticosterone regulation in an immature rat model of continuous chronic stress
Gilles, E. E., Schultz, L., & Baram, T. Z. (1996) · Pediatric Neurology · doi:10.1016/0887-8994(96)00153-1 · Cited by 199
Self-citationStructural changes at dendritic spine synapses during long-term potentiation
Harris, K. M., Fiala, J. C., & Ostroff, L. (2003) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2002.1254 · Cited by 180
Glucocorticoid toxicity in the hippocampus: Temporal aspects of neuronal vulnerability
Sapolsky, R. M. (1985) · Brain Research · doi:10.1016/0006-8993(85)91440-4 · Cited by 179
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
Self-citationEvidence for synaptic potentiation in a cortical network during learning
Roman, F. S., Staubli, U. V., & LYNCH, G. S. (1987) · Brain Research · doi:10.1016/0006-8993(87)90089-8 · Cited by 174
Self-citationKőrösi, A., Shanabrough, M., McClelland, S., Liu, Z.-W., Borók, E., Gao, X., Horváth, T. L., & Baram, T. Z. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4214-09.2010 · Cited by 174
Self-citationChen, Y., Bender, R. A., Brunson, K. L., Pomper, J. K., Grigoriadis, D. E., Wurst, W., & Baram, T. Z. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403975101 · Cited by 166
Self-citationThe Role of CRF in Behavioral Aspects of Stress
Heinrichs, S. C., Menzaghi, F., Pich, E. M., Britton, K. T., & Koob, G. F. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44673.x · Cited by 160
Avishai‐Eliner, S., Eghbal-Ahmadi, M., Tabachnik, E., Brunson, K. L., & Baram, T. Z. (2001) · Endocrinology · doi:10.1210/endo.142.1.7917 · Cited by 144
Chen, Y., Bender, R. A., Frotscher, M., & Baram, T. Z. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-18-07171.2001 · Cited by 140
Self-citationAvishai‐Eliner, S., Gilles, E. E., Eghbal‐Ahmadi, M., Bar‐El, Y., & Baram, T. Z. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00698.x · Cited by 139
Self-citationBeneficial effects of enriched environment following status epilepticus in immature rats
Faverjon, S., Silveira, D. C., Fu, D., Cha, B. H., Akman, Ç. I., Hu, Y., & Holmes, G. L. (2002) · Neurology · doi:10.1212/01.wnl.0000033588.59005.55 · Cited by 136
Reyes, B. A. S., Valentino, R. J., & Bockstaele, E. J. V. (2007) · Endocrinology · doi:10.1210/en.2007-0705 · Cited by 134
Brunson, K. L., Khan, N., Eghbal-Ahmadi, M., & Baram, T. Z. (2001) · Annals of Neurology · doi:10.1002/ana.66 · Cited by 129
Self-citationFenoglio, K. A., Brunson, K. L., Avishai-Eliner, S., Stone, B. A., Kapadia, B. J., & Baram, T. Z. (2005) · Endocrinology · doi:10.1210/en.2004-1285 · Cited by 119
Self-citationRegulation of stress-induced transcriptional changes in the hypothalamic neurosecretory neurons
Kovács, K. J., & Sawchenko, P. E. (1996) · Journal of Molecular Neuroscience · doi:10.1007/bf02736792 · Cited by 119
RIVIER, C. L., Grigoriadis, D. E., & Rivier, J. (2003) · Endocrinology · doi:10.1210/en.2002-0117 · Cited by 108
Self-citationCellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent
Chen, Y., Fenoglio, K. A., Dubé, C. M., Grigoriadis, D. E., & Baram, T. Z. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001863 · Cited by 98
Self-citationImpaired Recognition of the Goal Location during Spatial Navigation in Rats with Hippocampal Lesions
Hollup, S., Kjelstrup, K. B., Hoff, J., Moser, M., & Moser, E. I. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04505.2001 · Cited by 91
Akana, S. F., Jacobson, L., Cascio, C. S., Shinsako, J., & Dallman, M. F. (1988) · Endocrinology · doi:10.1210/endo-122-4-1337 · Cited by 78
Brunson, K. L., Grigoriadis, D. E., Lorang, M. T., & Baram, T. Z. (2002) · Experimental Neurology · doi:10.1006/exnr.2002.7937 · Cited by 74
Self-citationRegulation of Synaptic Transmission by CRF Receptors
Orozco-Cabal, L. F., Pollandt, S., Liu, J., Shinnick‐Gallagher, P., & Gallagher, J. P. (2006) · Reviews in the Neurosciences · doi:10.1515/revneuro.2006.17.3.279 · Cited by 73
Role of corticosteroid hormones in the dentate gyrus
Joëls, M. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)63021-0 · Cited by 67
Age‐Dependent Alterations in the Operations of Hippocampal Neural Networksa
Swann, J. W., Smith, K. L., & Brady, R. J. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb25930.x · Cited by 67
Merali, Z., Anisman, H., James, J. S., Kent, P., & Schulkin, J. A. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06281.x · Cited by 54
Rapid axon sprouting in the neonatal rat hippocampus
Gall, C. M., & LYNCH, G. S. (1978) · Brain Research · doi:10.1016/0006-8993(78)90415-8 · Cited by 50
Self-citationPitkänen, A., Nissinen, J., Łukasiuk, K., Jutila, L., Paljärvi, L., Salmenpera, T. M., Karkola, K. O., Vapalahti, M. P., & Ylinen, A. (2000) · Epilepsia · doi:10.1111/j.1528-1157.2000.tb01552.x · Cited by 42
Effects of olanzapine and quetiapine on corticotropin-releasing hormone release in the rat brain
Tringali, G., Lisi, L., Simone, M. L. D., Aubry, J., Preziosi, P., Pozzoli, G., & Navarra, P. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.05.012 · Cited by 16
Recognising childhood neuropsychiatric disorders.
Wilson, P. (2007) · PubMed · Cited by 3
Bayraktar (2000) · doi:10.1002/(sici)1096-9861(20000508)420:3
Self-citationEpisodic memory, semantic memory, and amnesia
Squire, L. R., & Zola, S. M. (1998) · Hippocampus · doi:10.1002/(sici)1098-1063(1998)8:3
Self-citation(1953) · Europe PMC (PubMed Central)
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McLaughlin, K. A., Weissman, D., & Bitrán, D. (2019) · Annual Review of Developmental Psychology · doi:10.1146/annurev-devpsych-121318-084950 · Cited by 892
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Dimensions of early experience and neural development: deprivation and threat
Sheridan, M. A., & McLaughlin, K. A. (2014) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2014.09.001 · Cited by 697
Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure
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Metadata
- Authors
- Ivy, A. S., Rex, C. S., Chen, Y., Dubé, C., Maras, P. M., Grigoriadis, D. E., Gall, C. M., Lynch, G., & Baram, T. Z.
- Affiliations
- University of California, Irvine (US)
- Neurocrine Biosciences (United States) (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-09-29
- Volume
- 30
- Issue
- 39
- Pages
- 13005-13015
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2991143
- OpenAlex
- W2080496806
- Cited by
- 402
- References
- 70
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 27 · 2023: 25 · 2022: 34 · 2021: 21 · 2020: 26 · 2019: 31 · 2018: 20 · 2017: 29 · 2016: 24 · 2015: 26 · 2014: 39 · 2013: 18 · 2012: 28
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (NS045260)
- National Institute on Aging (AG00358)
- National Institute of Mental Health (MH087467, F31MH087467, MH73136, R01MH073136)
- National Institute of Neurological Disorders and Stroke (P01NS045260, NS 28912, NS045260, R01NS028912, NS051823, R01NS051823, T32NS045540)
- 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
- hippocampal dysfunction, corticotropin-releasing factor, CRF1 receptor, dendritic atrophy, long-term potentiation, learning and memory impairment, novel object recognition, Morris water maze, CRF1 receptor antagonist, hippocampal interneurons, middle-aged rats, organotypic slice cultures
- MeSH terms
- CRF Receptor, Type 1, Animals, Animals, Newborn, Chronic Disease, Cognition Disorders, Corticotropin-Releasing Hormone, Disease Models, Animal, Female, Hippocampus, Humans, Male, Mice, Transgenic, Neurons, Organ Culture Techniques, Stress, Psychological, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Mice, Rats
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