Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex

Brown, Sarah M.; Henning, Shannon; Wellman, Cara L.

doi:10.1093/cercor/bhi048

Cited by 335Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex

Brown, Sarah M., Henning, Shannon, Wellman, Cara L.·2005·Cerebral Cortex

DOI 10.1093/cercor/bhi048

Open this paper in CoChat — free account

Abstract

Prefrontal cortex is a target for glucocorticoids, shows neurochemical changes in response to stress and mediates many of the behaviors that are altered by chronic corticosterone administration. Three weeks of either daily corticosterone injections or 3 h daily restraint stress result in dendritic changes in pyramidal neurons in medial prefrontal cortex. Interestingly, vehicle injection results in similar but less pronounced changes. Thus, the mild stress of daily injections alone may alter morphology of medial prefrontal cortex, suggesting an exquisite sensitivity to chronic stress. To further examine this morphological sensitivity, we assessed the effect of 1 week of daily brief restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were restrained 10 min per day for one week, handled daily or left unhandled. Rats were then overdosed and brains were stained using a Golgi-Cox procedure. Layer II-III pyramidal neurons in medial prefrontal cortex were drawn and dendritic morphology was quantified. One week of daily brief restraint resulted in selective remodeling of apical dendrites, with atrophy of up to 22-35% in distal branches and sparing of proximal branches. This pattern of reorganization is similar to that seen after either corticosterone injections or 3 weeks of daily 3 h restraint stress. Thus, the stress-induced dendritic changes in medial prefrontal cortex occur rapidly, and in response to a mild stressor.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1093/cercor/bhi048

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Structural changes in the hippocampus require several weeks of stress exposure, whereas dendrites in the PFC begin to change after only one week of stress or possibly even a single exposure.
“Whereas structural changes in the hippocampus require several weeks of stress exposure35, dendrites in the PFC begin to change after only one week of stress110 or possibly even a single exposure111.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [110]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Failure to escape traumatic shock.
Seligman, M. E., & Maier, S. F. (1967) · Journal of Experimental Psychology · doi:10.1037/h0024514 · Cited by 1,981 · cited 2× · see citing works
“For instance, several studies have demonstrated stress-induced deficits on a variety of cognitive tasks, including shuttle escape (Seligman and Maier, 1967), water maze (Altenor et al.”
Background
Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons
Watanabe, Y., Gould, E., & McEwen, B. S. (1992) · Brain Research · doi:10.1016/0006-8993(92)91597-8 · Cited by 1,212 · see citing works
Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex
Radley, J. J., Sisti, H. M., Hao, J., Rocher, A. B., McCall, T., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.01.006 · Cited by 769 · see citing works
Crises and Life Changes and the Onset of Schizophrenia
Brown, G. W., & Birley, J. L. T. (1968) · Journal of Health and Social Behavior · doi:10.2307/2948405 · Cited by 680 · see citing works
Stress Preferentially Increases Extraneuronal Levels of Excitatory Amino Acids in the Prefrontal Cortex: Comparison to Hippocampus and Basal Ganglia
Moghaddam, B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb13387.x · Cited by 567 · see citing works
Stress‐Induced Sensitization of Dopamine and Norepinephrine Efflux in Medial Prefrontal Cortex of the Rat
Gresch, P. J., Sved, A. F., Zigmond, M. J., & Finlay, J. M. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63020575.x · Cited by 179 · see citing works
Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala
Mark, G. P., Rada, P. V., & Shors, T. J. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00211-4 · Cited by 149 · see citing works
Corticotropin-Releasing Factor and Acute Stress Prolongs Serotonergic Regulation of GABA Transmission in Prefrontal Cortical Pyramidal Neurons
Tan, H., Zhong, P., & Yan, Z. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0143-04.2004 · Cited by 112 · see citing works

Flagged first, then by citations

Research works printed but not linked: 7

Berman KF, Weinberger DR (1999) Neuroimaging studies of schizo- phrenia. In: Neurobiology of mental illness (Charney DS, Nestler EJ, Bunney BS, eds), pp. 246--257. New York: Oxford University Press.
Brown GW, Harris TO (1989) Depression. In: Life events and illness (Brown GW, Harris TO, eds), pp. 49--93. New York: Guilford.
Cajal Sry (1995) Histology of the nervous system. New York: Oxford University Press.
Huttenlocher PR (1994) Synaptogenesis in human cerebral cortex. In: Human behavior and the developing brain (Dawson G, Fischer KW, eds), pp. 137--152. New York: Guilford Press.
Kolb B (1984) Functions of the frontal cortex of the rat: a comparative review. Brain Res Rev 8:65--98.
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. New York: Academic Press.
Zilles K, Wree A (1995) Cortex: areal and laminar structure. In: The rat nervous system (Paxinos G, ed.), pp. 649--685. San Diego: Academic Press.

Sorted by citations

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 · see citing works
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators
McEwen, B. S. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.071 · Cited by 1,864 · see citing works
Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease
McEwen, B. S., & Gianaros, P. J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05331.x · Cited by 1,715 · see citing works
Neural Mechanisms of Extinction Learning and Retrieval
Quirk, G. J., & Mueller, D. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301555 · Cited by 1,645 · see citing works
Protective and damaging effects of stress mediators: central role of the brain
McEwen, B. S. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/bmcewen · Cited by 1,220 · see citing works
The prefrontal cortex as a key target of the maladaptive response to stress
Cerqueira, J. J., Mailliet, F., Almeida, O. F. X., Jay, T. M., & Sousa, N. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4372-06.2007 · Cited by 599 · see citing works
Stress-induced prefrontal reorganization and executive dysfunction in rodents
Holmes, A., & Wellman, C. L. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.11.005 · Cited by 469 · see citing works
Self-citation
Brief Uncontrollable Stress Causes Dendritic Retraction in Infralimbic Cortex and Resistance to Fear Extinction in Mice
Izquierdo, A., Wellman, C. L., & Holmes, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0474-06.2006 · Cited by 459 · see citing works
Self-citation
Brain-Derived Neurotrophic Factor Val66Met Allele Impairs Basal and Ketamine-Stimulated Synaptogenesis in Prefrontal Cortex
Liu, R.-J., Lee, F. S., Li, X.-Y., Bambico, F., Duman, R. S., & Aghajanian, G. K. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.030 · Cited by 403 · see citing works
Neural control of chronic stress adaptation
Herman, J. P. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00061 · Cited by 384 · see citing works
Chronic stress: Implications for neuronal morphology, function and neurogenesis
Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.04.001 · Cited by 381 · see citing works
Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions
Ansell, E. B., Rando, K., Tuit, K., Guarnaccia, J., & Sinha, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.11.022 · Cited by 354 · see citing works
Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy
Liu, R.-J., & Aghajanian, G. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706679105 · Cited by 346 · see citing works
The Role of BDNF in Depression on the Basis of Its Location in the Neural Circuitry
Yu, H., & Chen, Z.-Y. (2011) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.184 · Cited by 343 · see citing works
Reversibility of apical dendritic retraction in the rat medial prefrontal cortex following repeated stress
RADLEY, J., ROCHER, A., JANSSEN, W., HOF, P., MCEWEN, B., & MORRISON, J. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.07.008 · Cited by 323 · see citing works
Stress, anxiety, and dendritic spines: What are the connections?
Leuner, B., & Shors, T. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.021 · Cited by 284 · see citing works
Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy
Murmu, M. S., Salomon, S., Biala, Y., Weinstock, M., Braun, K., & Bock, J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05024.x · Cited by 278 · see citing works
Spine synapse remodeling in the pathophysiology and treatment of depression
Duman, C. H., & Duman, R. S. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.022 · Cited by 257 · see citing works
Effect of brain‐derived neurotrophic factor haploinsufficiency on stress‐induced remodeling of hippocampal neurons
Magariños, A. M., Li, C. J., Gal Toth, J., Bath, K. G., Jing, D., Lee, F. S., & McEwen, B. S. (2011) · Hippocampus · doi:10.1002/hipo.20744 · Cited by 232 · see citing works
Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress
Hains, A. B., Vu, M. A. T., Maciejewski, P. K., van Dyck, C. H., Gottron, M., & Arnsten, A. F. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908563106 · Cited by 234 · see citing works
Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory
McCormick, C. M., & Mathews, I. Z. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.09.019 · Cited by 230 · see citing works
Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat
Sairanen, M., O’Leary, O. F., Knuuttila, J. E., & Castrén, E. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.069 · Cited by 206 · see citing works
Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder
Kapczinski, F., Frey, B. N., Kauer-Sant’Anna, M., & Grassi-Oliveira, R. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.7.1101 · Cited by 181 · see citing works
The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: Implications for hippocampal volume reductions in depression
Tata, D. A., & Anderson, B. J. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.09.008 · Cited by 173 · see citing works
“Like the hippocampus, the frontal lobe dysfunction has been implicated in depression [29-31] and the frontal lobe, like the hippocampus undergoes structural modification in response to glucocorticoids and stress [32-35].”
Background
Psychedelics and Other Psychoplastogens for Treating Mental Illness.
Vargas, M. V., Meyer, R., Avanes, A. A., Rus, M., & Olson, D. E. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.727117 · Cited by 166 · see citing works
Disconnection and reconnection: The morphological basis of (mal)adaptation to stress
Sousa, N., & Almeida, O. F. X. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.08.006 · Cited by 159 · see citing works
NMDA Receptor Blockade Alters Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex
Martin, K. P., & Wellman, C. L. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr021 · Cited by 138 · see citing works
Self-citation
Molecular mechanisms of stress-induced prefrontal cortical impairment: Implications for mental illness
Hains, A. B., & Arnsten, A. F. T. (2008) · Learning & Memory · doi:10.1101/lm.921708 · Cited by 127 · see citing works
Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction
Wilber, A. A., Walker, A. G., Southwood, C. J., Farrell, M. R., Lin, G. L., Rebec, G. V., & Wellman, C. L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.070 · Cited by 115 · see citing works
Self-citation
Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory.
Mika, A., Mazur, G. J., Hoffman, A. N., Talboom, J. S., Bimonte-Nelson, H. A., Sanabria, F., & Conrad, C. D. (2012) · Behavioral Neuroscience · doi:10.1037/a0029642 · Cited by 104 · see citing works
Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment
Krugers (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00024 · Cited by 102 · see citing works
Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex
Michelsen, K. A., van den Hove, D. L., Schmitz, C., Segers, O., Prickaerts, J., & Steinbusch, H. W. (2007) · BMC Neuroscience · doi:10.1186/1471-2202-8-107 · Cited by 100 · see citing works
Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex
Varea, E., Blasco-Ibáñez, J. M., Gómez-Climent, M. Á., Castillo-Gómez, E., Crespo, C., Martínez-Guijarro, F. J., & Nácher, J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301183 · Cited by 96 · see citing works
Functional and Structural Remodeling of Glutamate Synapses in Prefrontal and Frontal Cortex Induced by Behavioral Stress
Musazzi, L., Treccani, G., & Popoli, M. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00060 · Cited by 83 · see citing works
Adverse childhood experiences are associated with self-regulation and the magnitude of the error-related negativity difference
Lackner, C. L., Santesso, D. L., Dywan, J., O’Leary, D. D., Wade, T. J., & Segalowitz, S. J. (2018) · Biological Psychology · doi:10.1016/j.biopsycho.2018.01.006 · Cited by 60 · see citing works
Learning-induced alterations in prefrontal cortical dendritic morphology
Comeau, W. L., McDonald, R. J., & Kolb, B. E. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.04.033 · Cited by 53 · see citing works
Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects
Na, K.-S., Won, E., Kang, J., Kim, A., Choi, S., Tae, W.-S., Kim, Y.-K., Lee, M.-S., Joe, S.-H., & Ham, B.-J. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.04.030 · Cited by 50 · see citing works
Elevated cortisol awakening response associated with early life stress and impaired executive function in healthy adult males
Butler, K., Klaus, K., Edwards, L., & Pennington, K. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.07.013 · Cited by 43 · see citing works
Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress
Moench, K. M., Maroun, M., Kavushansky, A., & Wellman, C. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.12.002 · Cited by 41 · see citing works
Self-citation
DNA Methyltransferases in Depression: An Update
Duan, Z., & Lu, J. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.538683 · Cited by 32 · see citing works
Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations
Bisaz, R., & Sandi, C. (2012) · Stress · doi:10.3109/10253890.2011.608226 · Cited by 28 · see citing works
Adolescent nicotine exposure induces long-term, sex-specific disturbances in mood and anxiety-related behavioral, neuronal and molecular phenotypes in the mesocorticolimbic system
Ng, T. H. J., Sarikahya, M. H., Hudson, R., Szkudlarek, H. J., Pérez-Valenzuela, E., Uzuneser, T. C., Proud, E., Gummerson, D., Youssef, M., Machado, M., et al. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01853-y · Cited by 23 · see citing works
Reboxetine improves auditory attention and increases norepinephrine levels in the auditory cortex of chronically stressed rats
Pérez-Valenzuela, C., Gárate-Pérez, M. F., Sotomayor-Zárate, R., Delano, P. H., & Dagnino-Subiabre, A. (2016) · Frontiers in Neural Circuits · doi:10.3389/fncir.2016.00108 · Cited by 17 · see citing works

Authors: Brown, S. M., Henning, S., & Wellman, C. L.
Affiliations: Indiana University Bloomington (US)
Corresponding author: Brown, Sarah M.
ORCID: Brown, Sarah M.
Wellman, Cara L.
Venue: Cerebral Cortex
Publisher: Oxford University Press (OUP)
Published: 2005-02-09
Volume: 15
Issue: 11
Pages: 1714-1722
ISSN: 1047-3211 (ISSN-L)
1460-2199
DOI: 10.1093/cercor/bhi048
OpenAlex: W2130958493
Cited by: 335
References: 8
Citations by year: 2026: 4 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 13 · 2020: 16 · 2019: 22 · 2018: 18 · 2017: 20 · 2016: 18 · 2015: 15 · 2014: 17 · 2013: 21 · 2012: 21
FWCI: 7.51
Type: journal article
Language: en
Open access: closed
Locations: Cerebral Cortex (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
Directorate for Biological Sciences
National Institute of Mental Health (R03MH067607, MH 067607)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: dendritic morphology, medial prefrontal cortex, restraint stress, chronic stress, corticosterone, glucocorticoids, pyramidal neurons, dendritic atrophy, apical dendrites, Golgi-Cox staining
MeSH terms: Adaptation, Physiological, Animals, Corticosterone, Dendrites, Male, Neuronal Plasticity, Restraint, Physical, Stress, Physiological, Rats, Sprague-Dawley, Prefrontal Cortex, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Record

About these checks