Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Hains, Avis Brennan; Vu, Mai Anh T.; Maciejewski, Paul K.; van Dyck, Christopher H.; Gottron, Melissa; Arnsten, Amy F. T.

doi:10.1073/pnas.0908563106

Cited by 234Neuroscience and Neuropharmacology ResearchStress Responses and CortisolMemory and Neural Mechanisms

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Open access

Hains, Avis Brennan, Vu, Mai Anh T., Maciejewski, Paul K., van Dyck, Christopher H., Gottron, Melissa, Arnsten, Amy F. T.·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0908563106PMC PMC2742406

Open this paper in CoChat — free account

Abstract

The prefrontal cortex r regulates behavior, cognition, and emotion by using working memory. Prefrontal functions are impaired by stress exposure. Acute, stress-induced deficits arise from excessive protein kinase C (PKC) signaling, which diminishes prefrontal neuronal firing. Chronic stress additionally produces architectural changes, reducing dendritic complexity and spine density of cortico-cortical pyramidal neurons, thereby disrupting excitatory working memory networks. In vitro studies have found that sustained PKC activity leads to spine loss from hippocampal-cultured neurons, suggesting that PKC may contribute to spine loss during chronic stress exposure. The present study tested whether inhibition of PKC with chelerythrine before daily stress would protect prefrontal spines and working memory. We found that inhibition of PKC rescued working memory impairments and reversed distal apical dendritic spine loss in layer II/III pyramidal neurons of rat prelimbic cortex. Greater spine density predicted better cognitive performance, the first direct correlation between pyramidal cell structure and working memory abilities. These findings suggest that PKC inhibitors may be neuroprotective in disorders with dysregulated PKC signaling such as bipolar disorder, schizophrenia, post-traumatic stress disorder, and lead poisoning—conditions characterized by impoverished prefrontal structural and functional integrity.

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 · 10.1073/pnas.0908563106

Cites

67 of 67 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?

Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC).
“Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC), a recently evolved brain region that provides top-down regulation of thought, action, and emotion.”
From Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. (2021) · cites this paper as [16]
The Abstract reports that repeated stress causes dendritic retraction and loss of spine density in the PFC, and the Discussion reports similar changes under chronic restraint stress in rats. The paper describes *acute* stress as uncontrollable, but does not establish that qualifier for the chronic stress associated with spine and dendrite loss. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Guanfacine inhibits feedforward Ca2+-cAMP-PKA-K+ actions that weaken PFC network connectivity, neuronal firing and function.
“stress increases, while guanfacine inhibits, the feedforward Ca2+-cAMP-PKA-K+ actions that weaken PFC network connectivity, neuronal firing and function.”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Hains et al., 2009
The Discussion (page unavailable) describes Ca2+–cAMP and PI–PKC feed-forward interactions that may amplify the stress response, and the Abstract says excessive PKC signaling diminishes prefrontal neuronal firing. But the paper identifies chelerythrine, not guanfacine, as the inhibitor studied; these passages do not establish that guanfacine inhibits the specified Ca2+–cAMP–PKA–K+ actions. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Stress increases feedforward Ca2+-cAMP-PKA-K+ actions that weaken PFC network connectivity, neuronal firing and function.
“stress increases, while guanfacine inhibits, the feedforward Ca2+-cAMP-PKA-K+ actions that weaken PFC network connectivity, neuronal firing and function.”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Hains et al., 2009
The Discussion (page not supplied) says Ca2+ can increase cAMP and that feed-forward interactions between cAMP and PI-PKC pathways may amplify the stress response. The paper also reports that stress-related PKC signaling diminishes prefrontal neuronal firing and that chronic stress disrupts working-memory networks. It does not establish the claimed Ca2+-cAMP-PKA-K+ sequence as the mechanism of those effects. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Loss of dendritic spines and/or dendrites is accompanied by, and often correlates with, loss of PFC cognitive functioning.
“Loss of dendritic spines and/or dendrites is accompanied by, and often correlates with, the loss of PFC cognitive functioning.”
From Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. (2021) · cites this paper as [16]
Chronic stress exposure causes loss of dendritic spines from layer II/III pyramidal cells in rat mPFC.
“With chronic stress exposure, dendritic spines are lost from layer II/III pyramidal cells in rat mPFC”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Hains et al., 2009

Inhibition of PKC or PKA signaling can prevent loss of mPFC dendritic spines and working memory abilities during chronic stress exposure.
“Research in rats by Avis Hains has shown that inhibition of PKC or PKA signaling can prevent the loss of mPFC dendritic spines and working memory abilities during chronic stress exposure (Hains et al., 2009, Hains et al., 2015), suggesting that the sustained weakening of synaptic connectivity via K+ channel opening contributes to spine loss.”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Hains et al., 2009
With chronic stress exposure, there is architectural loss of mPFC spines and dendrites that correlates with impaired PFC cognitive functioning.
“With chronic stress exposure, there is architectural loss of mPFC spines and dendrites (Moda-Sava et al., 2019, Radley et al., 2006) that correlates with impaired PFC cognitive functioning (Hains et al., 2009, Hains et al., 2015, Liston et al., 2006).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Hains et al., 2009
Dendritic spine loss from layer II/III pyramidal cells in the prelimbic medial PFC correlates with impaired working memory on the delayed alternation task.
“Dendritic spine loss from layer II/III pyramidal cells in the prelimbic medial PFC correlates with impaired working memory on the delayed alternation task75.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [75]
The protection of dendritic spines correlates with preserved working memory function.
“The protection of dendritic spines correlates with preserved working memory function75.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [75]
Inhibition of PKC signaling before daily stress exposure in rats prevents the loss of spines from layer II/III PFC pyramidal cells normally observed with chronic stress.
“Inhibition of PKC signaling before daily stress exposure in rats prevents the loss of spines from layer II/III PFC pyramidal cells normally observed with chronic stress75.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [75]

Self-check

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

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

Cellular basis of working memory
Goldman-Rakic, P. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90304-6 · Cited by 2,663 · see citing works
Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders
MCEWEN, B. S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1314.001 · Cited by 1,638 · see citing works
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636 · see citing works
Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS
Green, M. F., Kern, R. S., & Heaton, R. K. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.09.009 · Cited by 1,422 · see citing works
Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates
Dalley, J. W., Cardinal, R. N., & Robbins, T. W. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.09.006 · Cited by 1,329 · see citing works
Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory
Vijayraghavan, S., Wang, M., Birnbaum, S. G., Williams, G. V., & Arnsten, A. F. T. (2007) · Nature Neuroscience · doi:10.1038/nn1846 · Cited by 1,013 · see citing works
Self-citation
Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set-Shifting
Liston, C., Miller, M. M., Goldwater, D. S., Radley, J. J., Rocher, A. B., Hof, P. R., Morrison, J. H., & McEwen, B. S. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1184-06.2006 · Cited by 968 · see citing works
Psychosocial stress reversibly disrupts prefrontal processing and attentional control
Liston, C., McEwen, B. S., & Casey, B. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807041106 · Cited by 859 · see citing works
Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex
Radley, J. J., Rocher, A. B., Miller, M., Janssen, W. G. M., Liston, C., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhi104 · Cited by 820 · 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
Chronic stress alters dendritic morphology in rat medial prefrontal cortex
Cook, S. C., & Wellman, C. L. (2004) · Journal of Neurobiology · doi:10.1002/neu.20025 · Cited by 750 · see citing works
Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study.
Bremner, J., Staib, L., Kaloupek, D., Southwick, S., Soufer, R., & Charney, D. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00297-2 · Cited by 730 · see citing works
A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder
Baum, A. E., Akula, N., Cabanero, M., Cardona, I., Corona, W., Klemens, B., Schulze, T. G., Cichon, S., Rietschel, M., Nöthen, M. M., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002012 · Cited by 700 · see citing works
Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex
Qin, S., Hermans, E. J., van Marle, H. J. F., Luo, J., & Fernández, G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.006 · Cited by 675 · see citing works
α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex
Wang, M., Ramos, B. P., Paspalas, C. D., Shu, Y., Simen, A., Duque, A., Vijayraghavan, S., Brennan, A., Dudley, A., Nou, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.015 · Cited by 672 · see citing works
Self-citation
Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy
Conrad, C. D., Magariños, A. M., LeDoux, J. E., & McEwen, B. S. (1999) · Behavioral Neuroscience · doi:10.1037/0735-7044.113.5.902 · Cited by 664 · see citing works
Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy.
Conrad, C. D., Magariños, A. M., LeDoux, J. E., & McEwen, B. S. (1999) · Behavioral Neuroscience · doi:10.1037//0735-7044.113.5.902 · Cited by 663 · see citing works
Lithium-induced increase in human brain grey matter
Moore, G. J., Bebchuk, J. M., Wilds, I. B., Chen, G., & Menji, H. K. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02793-8 · Cited by 649 · see citing works
Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration
Wellman, C. L. (2001) · Journal of Neurobiology · doi:10.1002/neu.1079 · Cited by 594 · see citing works
Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys
Murphy, B. L., Arnsten, A. F., Goldman-Rakic, P. S., & Roth, R. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1325 · Cited by 590 · see citing works
Self-citation
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick, S. M., Bremner, J. D., Rasmusson, A., Morgan, C. A., Arnsten, A., & Charney, D. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00219-x · Cited by 573 · see citing works
Self-citation
Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children
Braun, J. M., Kahn, R. S., Froehlich, T., Auinger, P., & Lanphear, B. P. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.9478 · Cited by 573 · see citing works
Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency
Peroutka, S. J., & Synder, S. H. (1980) · American Journal of Psychiatry · doi:10.1176/ajp.137.12.1518 · Cited by 544 · see citing works
Association of Prenatal and Childhood Blood Lead Concentrations with Criminal Arrests in Early Adulthood
Wright, J. P., Dietrich, K. N., Ris, M. D., Hornung, R. W., Wessel, S. D., Lanphear, B. P., Ho, M., & Rae, M. N. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050101 · Cited by 467 · see citing works
Decreased Brain Volume in Adults with Childhood Lead Exposure
Cecil, K. M., Brubaker, C. J., Adler, C. M., Dietrich, K. N., Altaye, M., Egelhoff, J. C., Wessel, S., Elangovan, I., Hornung, R., Jarvis, K., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050112 · Cited by 458 · see citing works
Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia
Mirnics, K., Middleton, F. A., Stanwood, G. D., Lewis, D. A., & Levitt, P. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000866 · Cited by 446 · see citing works
Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates.
Goldman-Rakic, P. (1990) · Progress in Brain Research · doi:10.1016/s0079-6123(08)62688-6 · Cited by 443 · see citing works
Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam
Finlay, J. M., Zigmond, M. J., & Abercrombie, E. D. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00331-x · Cited by 434 · see citing works
Protein kinase C and the regulation of the actin cytoskeleton
Larsson, C. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.07.010 · Cited by 388 · see citing works
Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex
Radley, J. J., Rocher, A. B., Rodriguez, A., Ehlenberger, D. B., Dammann, M., McEwen, B. S., Morrison, J. H., Wearne, S. L., & Hof, P. R. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21588 · Cited by 374 · see citing works
How Lead Exposure Relates to Temporal Changes in IQ, Violent Crime, and Unwed Pregnancy
Nevin, R. (2000) · Environmental Research · doi:10.1006/enrs.1999.4045 · Cited by 365 · see citing works
Kinetic Properties of “Soluble” Adenylyl Cyclase
Litvin, T. N., Kamenetsky, M., Zarifyan, A. S., Buck, J., & Levin, L. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212475200 · Cited by 346 · see citing works
Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex
Brown, S. M., Henning, S., & Wellman, C. L. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi048 · Cited by 335 · see citing works
Protein kinase C overactivity impairs prefrontal cortical regulation of working memory
Birnbaum, S. G., Yuan, P. X., Wang, M., Vijayraghavan, S., Bloom, A. K., Davis, D. J., Gobeske, K. T., Sweatt, J. D., Manji, H. K., & Arnsten, A. F. T. (2004) · Science · doi:10.1126/science.1100021 · Cited by 318 · see citing works
Self-citation
Greater Cortical Gray Matter Density in Lithium-Treated Patients with Bipolar Disorder
Bearden, C. E., Thompson, P. M., Dalwani, M., Hayashi, K. M., Lee, A. D., Nicoletti, M., Trakhtenbroit, M., Glahn, D. C., Brambilla, P., Sassi, R. B., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.10.027 · Cited by 289 · see citing works
Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manic-depressive illness
Manji, H. K., & Lenox, R. H. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00235-8 · Cited by 241 · see citing works
Lead-calcium interactions in cellular lead toxicity.
Legare, M. E., Castiglioni, A. J., Rowles, T. K., Calvin, J. A., Snyder-Armstead, C., & Tiffany-Castiglioni, E. (1993) · PubMed · Cited by 240 · see citing works
Perseveration and Strategy in a Novel Spatial Self-Ordered Sequencing Task for Nonhuman Primates: Effects of Excitotoxic Lesions and Dopamine Depletions of the Prefrontal Cortex
Collins, P., Roberts, A., Dias, R. S., Everitt, B. J., & Robbins, T. W. (1998) · Journal of Cognitive Neuroscience · doi:10.1162/089892998562771 · Cited by 229 · see citing works
Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment
Wood, G. E., Young, L. T., Reagan, L. P., Chen, B., & McEwen, B. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400208101 · Cited by 197 · see citing works
Essential Role for the PKC Target MARCKS in Maintaining Dendritic Spine Morphology
Calabrese, B., & Halpain, S. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.027 · Cited by 187 · see citing works
Reexamination of functional subdivisions of the rodent prefrontal cortex
Eichenbaum, H., Clegg, R. A., & Feeley, A. (1983) · Experimental Neurology · doi:10.1016/0014-4886(83)90224-8 · Cited by 182 · see citing works
Age, Rapid-Cycling, and Pharmacotherapy Effects on Ventral Prefrontal Cortex in Bipolar Disorder: A Cross-Sectional Study
Blumberg, H. P., Krystal, J. H., Bansal, R., Martin, A., Dziura, J., Durkin, K., Martin, L., Gerard, E., Charney, D. S., & Peterson, B. S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.031 · Cited by 171 · see citing works
Evidence that lead acts as a calcium substitute in second messenger metabolism.
Goldstein, G. W. (1994) · PubMed · Cited by 170 · see citing works
Frontal lobe system and spatial reversal in the rat
Divac, I. (1971) · Neuropsychologia · doi:10.1016/0028-3932(71)90041-8 · Cited by 160 · see citing works
Neocortical Gray Matter Volume in First-Episode Schizophrenia and First-Episode Affective Psychosis: A Cross-Sectional and Longitudinal MRI Study
Nakamura, M., Salisbury, D. F., Hirayasu, Y., Sylvain Bouix, A., Pohl, K. M., Yoshida, T., Koo, M., Shenton, M. E., & McCarley, R. W. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.03.030 · Cited by 158 · see citing works
Daytime Prazosin Reduces Psychological Distress to Trauma Specific Cues in Civilian Trauma Posttraumatic Stress Disorder
Taylor, F. B., Lowe, K., Thompson, C. E., McFall, M., Peskind, E. R., Kanter, E. D., Allison, N., Williams, J., Martin, P., & Raskind, M. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.023 · Cited by 138 · see citing works
Structure of inositol monophosphatase, the putative target of lithium therapy.
Bone, R. F., Springer, J. P., & Atack, J. R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10031 · Cited by 135 · see citing works
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
Self-citation
In vivo potencies of antipsychotic drugs in blocking alpha 1 noradrenergic and dopamine D2 receptors: Implications for drug mechanisms of action
Cohen, B. M., & Lipinski, J. F. (1986) · Life Sciences · doi:10.1016/0024-3205(86)90111-6 · Cited by 125 · see citing works
α-Adrenoceptor modulation hypothesis of antipsychotic atypicality
Svensson, T. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.009 · Cited by 125 · see citing works
Molecular activity underlying working memoryPreprint
Dash, P. K., Moore, A. N., Kobori, N., & Runyan, J. D. (2007) · Learning & Memory · doi:10.1101/lm.558707 · Cited by 113 · see citing works
The effects of sex and hormonal status on restraint-stress-induced working memory impairment
Shansky, R. M., Rubinow, K., Brennan, A., & Arnsten, A. F. (2006) · Behavioral and Brain Functions · doi:10.1186/1744-9081-2-8 · Cited by 107 · see citing works
Self-citation
Chronic Stress Increases the Plasmalemmal Distribution of the Norepinephrine Transporter and the Coexpression of Tyrosine Hydroxylase in Norepinephrine Axons in the Prefrontal Cortex
Miner, L. H., Jedema, H. P., Moore, F. W., Blakely, R. D., Grace, A. A., & Sesack, S. R. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4450-05.2006 · Cited by 107 · see citing works
Daily injections alter spine density in rat medial prefrontal cortex
Seib, L. M., & Wellman, C. L. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(02)01287-9 · Cited by 100 · see citing works
Analysis of Differential Effects of Pb2+on Protein Kinase C Isozymes
Sun, X., Tian, X., Tomsig, J. L., & Suszkiw, J. B. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8622 · Cited by 99 · see citing works
Dendritic Spine Density in Schizophrenia and Depression
Glantz, L. A., & Lewis, D. A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.2.203 · Cited by 73 · see citing works
The type III inositol 1,4,5-trisphosphate receptor is phosphorylated by cAMP-dependent protein kinase at three sites
Soulsby, M. D., & Wojcikiewicz, R. J. H. (2005) · Biochemical Journal · doi:10.1042/bj20051325 · Cited by 71 · see citing works
A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory
Runyan, J. D., Moore, A. N., & Dash, P. K. (2005) · Learning & Memory · doi:10.1101/lm.89405 · Cited by 68 · see citing works
Dorsolateral prefrontal cortex morphology and short-term outcome in first-episode schizophrenia
Prasad, K. M. R., Sahni, S. D., Rohm, B. R., & Keshavan, M. S. (2005) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2004.05.009 · Cited by 65 · see citing works
Early lead exposure produces lasting changes in sustained attention, response initiation, and reactivity to errors
Morgan, R. E., Garavan, H., Smith, E. G., Driscoll, L. L., Levitsky, D. A., & Strupp, B. J. (2001) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(01)00171-4 · Cited by 58 · see citing works
Impact of Corticotropin‐Releasing Hormone on Extracellular Norepinephrine in Prefrontal Cortex After Chronic Cold Stress
Finlay, J. M., Jedema, H. P., Rabinovic, A. D., Mana, M. J., Zigmond, M. J., & Sved, A. F. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010144.x · Cited by 57 · see citing works
Protein kinase C activity is associated with prefrontal cortical decline in aging
Brennan, A. R., Yuan, P., Dickstein, D. L., Rocher, A. B., Hof, P. R., Manji, H. K., & Arnsten, A. F. T. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.08.020 · Cited by 47 · see citing works
Self-citation
An in-depth analysis of lead effects in a delayed spatial alternation task: Assessment of mnemonic effects, side bias, and proactive interference
Alber, S. A., & Strupp, B. J. (1996) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(95)02026-8 · Cited by 42 · see citing works
Effects of Treatment with Haloperidol, Chlorpromazine, and Clozapine on Protein Kinase C (PKC) and Phosphoinositide-Specific Phospholipase C (PI-PLC) Activity and on mRNA and Protein Expression of PKC and PLC Isozymes in Rat Brain
Dwivedi, Y., & Pandey, G. N. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35156-0 · Cited by 40 · see citing works
A rapid, nongenomic action of glucocorticoids in rat B103 neuroblastoma cells
Han, J.-Z., Lin, W., Lou, S.-J., Qiu, J., & Chen, Y.-Z. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00242-2 · Cited by 22 · see citing works
Mania: a Rational Neurobiology
Arnsten, A., & Manji, H. (2008) · Future Neurology · doi:10.2217/14796708.3.2.125 · Cited by 14 · see citing works
Self-citation
Noise Stress Impairs Prefrontal Cortical Cognitive Function in Monkeys: Evidence for a Hyperdopaminergic Mechanism
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.4.362 · Cited by 6 · see citing works
Self-citation

Flagged first, then by citations

Research works printed but not linked: 1

[59]Prasad KM, Sahni SD, Rohm BR, Keshavan MS. The type III inositol 1,4,5-trisphosphate receptor is phosphorylated by cAMP-dependent protein kinase at three sites. Psychiatry Res. 2005;140:147–155. [Google Scholar]

Sorted by citations

The Brain on Stress: Vulnerability and Plasticity of the Prefrontal Cortex over the Life Course
McEwen, B. S., & Morrison, J. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.028 · Cited by 1,079 · see citing works
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Self-citation
Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1731-10.2010 · Cited by 621 · see citing works
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581 · see citing works
Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses
Arnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
Self-citation
Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours
Makale, M., McDonald, C. R., Hattangadi-Gluth, J. A., & Kesari, S. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.185 · Cited by 533 · see citing works
Stress and cognition
Sandi, C. (2013) · Wiley Interdisciplinary Reviews Cognitive Science · doi:10.1002/wcs.1222 · Cited by 505 · see citing works
Dendritic Spines in Depression: What We Learned from Animal Models
Qiao, H., Li, M.-X., Xu, C. S., Chen, H.-B., An, S.-C., & Ma, X. (2016) · Neural Plasticity · doi:10.1155/2016/8056370 · Cited by 442 · see citing works
The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder
Arnsten, A. F. T., Raskind, M. A., Taylor, F. B., & Connor, D. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.10.002 · Cited by 381 · see citing works
Self-citation
Chronic stress and brain plasticity: Mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders
Radley, J., Morilak, D., Viau, V., & Campeau, S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.06.018 · Cited by 339 · see citing works
Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc
Gallo, F. T., Katche, C., Morici, J. F., Medina, J. H., & Weisstaub, N. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00079 · Cited by 339 · 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
Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling
Chen, 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 · see citing works
Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex
Bloss, E. B., Janssen, W. G., Ohm, D. T., Yuk, F. J., Wadsworth, S., Saardi, K. M., McEwen, B. S., & Morrison, J. H. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0839-11.2011 · Cited by 219 · see citing works
Atypical prefrontal connectivity in attention-deficit/hyperactivity disorder: pathway to disease or pathological end point?
Liston, C., Cohen, M. M., Teslovich, T., Levenson, D., & Casey, B. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.03.022 · Cited by 216 · see citing works
Can anxiety damage the brain?
Mah, L., Szabuniewicz, C., & Fiocco, A. J. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000223 · Cited by 206 · see citing works
Interactive Effects of Stress and Aging on Structural Plasticity in the Prefrontal Cortex
Bloss, E. B., Janssen, W. G. M., McEwen, B. S., & Morrison, J. H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0759-10.2010 · Cited by 185 · see citing works
Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases
Nguyen, L. D., & Ehrlich, B. E. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012075 · Cited by 176 · see citing works
Prefrontal cortical network connections: key site of vulnerability in stress and schizophrenia
Arnsten, A. F. T. (2011) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2011.02.006 · Cited by 172 · see citing works
Self-citation
Home Visiting and the Biology of Toxic Stress: Opportunities to Address Early Childhood Adversity
Garner, A. S. (2013) · PEDIATRICS · doi:10.1542/peds.2013-1021d · Cited by 163 · see citing works
β-Adducin Is Required for Stable Assembly of New Synapses and Improved Memory upon Environmental Enrichment
Bednarek, E., & Caroni, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.034 · Cited by 160 · see citing works
Dynamic network connectivity: a new form of neuroplasticity
Arnsten, A. F. T., Paspalas, C. D., Gamo, N. J., Yang, Y., & Wang, M. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.05.003 · Cited by 160 · see citing works
Self-citation
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Woo, E., Sansing, L. H., Arnsten, A. F. T., & Datta, D. (2021) · Chronic Stress · doi:10.1177/24705470211029254 · Cited by 159 · see citing works
Self-citation
Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling
Wang, X., Chen, Y., Wolf, M., Wagner, K. V., Liebl, C., Scharf, S. H., Harbich, D., Mayer, B., Wurst, W., Holsboer, F., et al. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.020 · Cited by 157 · see citing works
Depression: A repair response to stress-induced neuronal microdamage that can grade into a chronic neuroinflammatory condition?
Wager‐Smith, K., & Markou, A. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.09.010 · Cited by 150 · see citing works
Constellation of HCN Channels and cAMP Regulating Proteins in Dendritic Spines of the Primate Prefrontal Cortex: Potential Substrate for Working Memory Deficits in Schizophrenia
Paspalas, C. D., Wang, M., & Arnsten, A. F. T. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs152 · Cited by 136 · see citing works
Self-citation
Physician Distress and Burnout: The Neurobiological Perspective
Arnsten, A. F. T., & Shanafelt, T. D. (2021) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.12.027 · Cited by 135 · see citing works
Self-citation
Alterations in Corticolimbic Dendritic Morphology and Emotional Behavior in Cannabinoid CB1 Receptor-Deficient Mice Parallel the Effects of Chronic Stress
Hill, M. N., Hillard, C. J., & McEwen, B. S. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq280 · Cited by 127 · see citing works
Molecular modulation of prefrontal cortex: Rational development of treatments for psychiatric disorders.
Gamo, N. J., & Arnsten, A. F. T. (2011) · Behavioral Neuroscience · doi:10.1037/a0023165 · Cited by 124 · see citing works
Self-citation
Chronic Stress-Induced Alterations of Dendritic Spine Subtypes Predict Functional Decrements in an Hypothalamo–Pituitary–Adrenal-Inhibitory Prefrontal Circuit
Radley, J. J., Anderson, R. M., Hamilton, B. A., Alcock, J. A., & Romig‐Martin, S. A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0287-13.2013 · Cited by 121 · see citing works
Molecular regulation of dendritic spine dynamics and their potential impact on synaptic plasticity and neurological diseases
Maiti, P., Manna, J., Ilavazhagan, G., Rossignol, J., & Dunbar, G. L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.020 · Cited by 118 · see citing works
The gut microbiome modulates the transformation of microglial subtypes
Huang, Y., Wu, J., Zhang, H., Li, Y., Wen, L., Tan, X., Cheng, K., Liu, Y., Pu, J., Liu, L., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02017-y · Cited by 111 · 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
Stress during a critical postnatal period induces region-specific structural abnormalities and dysfunction of the prefrontal cortex via CRF1
Yang, X.-D., Liao, X.-M., Uribe-Mariño, A., Liu, R., Xie, X.-M., Jia, J., Su, Y.-A., Li, J.-T., Schmidt, M. V., Wang, X.-D., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.304 · Cited by 93 · see citing works
Inhibition of phosphodiesterase 2 reverses impaired cognition and neuronal remodeling caused by chronic stress
Xu, Y., Pan, J., Sun, J., Ding, L., Ruan, L., Reed, M. N., Yu, X., Klabnik, J., Lin, D., Li, J., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.028 · Cited by 92 · see citing works
Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction
Uribe-Mariño, A., Gassen, N. C., Wiesbeck, M. F., Balsevich, G., Santarelli, S., Solfrank, B., Dournes, C., Fries, G. R., Masana, M., Labermeier, C., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.03.2106 · Cited by 90 · see citing works
Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders
Hall, B. S., Moda, R. N., & Liston, C. M. (2014) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.10.008 · Cited by 90 · see citing works
Naloxone-Reversible Modulation of Pain Circuitry by Left Prefrontal rTMS
Taylor, J. J., Borckardt, J. J., Canterberry, M., Li, X., Hanlon, C. A., Brown, T. R., & George, M. S. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.13 · Cited by 89 · see citing works
Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology
McNamara, R. K. (2015) · World Journal of Psychiatry · doi:10.5498/wjp.v5.i1.15 · Cited by 88 · see citing works
Functional Contribution of the Medial Prefrontal Circuitry in Major Depressive Disorder and Stress-Induced Depressive-Like Behaviors
Bittar, T. P., & Labonté, B. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.699592 · Cited by 87 · see citing works
Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control
Joyce, M. K. P., Uchendu, S., & Arnsten, A. F. T. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.06.016 · Cited by 86 · see citing works
Self-citation
Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature
Saxena, A., Scaini, G., Bavaresco, D. V., Leite, C., Valvassoria, S. S., Carvalho, A. F., & Quevedo, J. (2017) · Complex Psychiatry · doi:10.1159/000480349 · Cited by 85 · 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
Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons
Ripamonti, S., Ambrozkiewicz, M. C., Guzzi, F., Gravati, M., Biella, G. R., Bormuth, I., Hammer, M., Tuffy, L. P., Sigler, A., Kawabe, H., et al. (2017) · eLife · doi:10.7554/elife.22466 · Cited by 82 · see citing works
Postnatal Serotonin Type 2 Receptor Blockade Prevents the Emergence of Anxiety Behavior, Dysregulated Stress-Induced Immediate Early Gene Responses, and Specific Transcriptional Changes that Arise Following Early Life Stress
Benekareddy, M., Vadodaria, K. C., Nair, A. R., & Vaidya, V. A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.08.005 · Cited by 79 · see citing works
Molecular Influences on Working Memory Circuits in Dorsolateral Prefrontal Cortex
Arnsten, A. F. T., & Jin, L. E. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-420170-5.00008-8 · Cited by 79 · see citing works
Self-citation
Loss of prefrontal cortical higher cognition with uncontrollable stress: molecular mechanisms, changes with age, and relevance to treatment
Datta, D., & Arnsten, A. (2019) · Brain Sciences · doi:10.3390/brainsci9050113 · Cited by 78 · see citing works
Self-citation
A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)'s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression
Li, Y., Pehrson, A. L., Waller, J. A., Dale, E., Sánchez, C., & Gulinello, M. E. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00279 · Cited by 78 · see citing works
Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuritogenesis and neuronal motility
Lang, B., Pu, J., Hunter, I., Liu, M., Martín‐Granados, C., Reilly, T. J., Gao, G., Guan, Z., Li, W., Shi, Y., et al. (2013) · Journal of Cell Science · doi:10.1242/jcs.137604 · Cited by 78 · see citing works
Transient inactivation of the infralimbic cortex induces antidepressant-like effects in the rat
Slattery, D. A., Neumann, I. D., & Cryan, J. F. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110368873 · Cited by 77 · see citing works
The nucleus reuniens: a key node in the neurocircuitry of stress and depression
Kafetzopoulos, V., Kokras, N., Sotiropoulos, I., Oliveira, J. F., Leite‐Almeida, H., Vassalou, A., Sardinha, V. M., Papadopoulou‐Daifoti, Z., Almeida, O. F. X., Antoniou, K., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.55 · Cited by 77 · see citing works
The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex
Arnsten, A. F. T., Datta, D., & Wang, M. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00973-3 · Cited by 76 · see citing works
Self-citation
Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species
Arnsten, A. F. T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107327 · Cited by 75 · see citing works
“, 2006) that correlates with impaired PFC cognitive functioning (Hains et al., 2009; Hains, Yabe, & Arnsten, 2015; Liston et al., 2006).”
Self-citation
Treadmill exercise suppressed stress-induced dendritic spine elimination in mouse barrel cortex and improved working memory via BDNF/TrkB pathway
Chen, K., Zhang, L., Tan, M., Lai, C. S. W., Li, A., Ren, C., & So, K. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.41 · Cited by 75 · see citing works
Chronic stimulation of alpha-2A-adrenoceptors with guanfacine protects rodent prefrontal cortex dendritic spines and cognition from the effects of chronic stress
Hains, A. B., Yabe, Y., & Arnsten, A. F. T. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.01.001 · Cited by 70 · see citing works
Self-citation
Lead (Pb) exposure induces dopaminergic neurotoxicity in Caenorhabditis elegans: Involvement of the dopamine transporter
Akinyemi, A. J., Miah, M. R., Ijomone, O. M., Tsatsakis, A. M., Soares, F. A. A., Tinkov, A. A., Skalny, A. V., Venkataramani, V., & Aschner, M. (2019) · Toxicology Reports · doi:10.1016/j.toxrep.2019.08.001 · Cited by 69 · see citing works
The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity
Diniz, C. R. A. F., & Crestani, A. P. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01931-x · Cited by 67 · see citing works
Differential dendritic remodeling in prelimbic cortex of male and female rats during recovery from chronic stress
Moench, K. M., & Wellman, C. L. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.05.049 · Cited by 63 · see citing works
Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro: Implication for antioxidative psychotropic actions via microglia
Kato, T. A., Monji, A., Yasukawa, K., Mizoguchi, Y., Horikawa, H., Seki, Y., Hashioka, S., Han, Y.-H., Kasai, M., Sonoda, N., et al. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.03.019 · Cited by 62 · see citing works
Stress induced neural reorganization: A conceptual framework linking depression and Alzheimer's disease
Ross, J. A., Gliebus, G. P., & Bockstaele, E. J. V. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.004 · Cited by 62 · see citing works
Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex
Anderson, R. M., Glanz, R. M., Johnson, S. B., Miller, M. M., Romig‐Martin, S. A., & Radley, J. J. (2016) · The Journal of Comparative Neurology · doi:10.1002/cne.24027 · Cited by 60 · see citing works
The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion
Arnsten, A. F. T., Joyce, M. K. P., & Roberts, A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.105000 · Cited by 58 · see citing works
Self-citation
Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula
Nuno‐Perez, A., Trusel, M., Lalive, A. L., Congiu, M., Gastaldo, D., Tchenio, A., Lecca, S., Soiza‐Reilly, M., Bagni, C., & Mameli, M. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.008 · Cited by 57 · see citing works
Effects of stress on the structure and function of the medial prefrontal cortex: Insights from animal models
Wellman, C. L., Bollinger, J. L., & Moench, K. M. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.11.007 · Cited by 53 · see citing works
Large effects of brief meditation intervention on EEG spectra in meditation novices
Stapleton, P., Dispenza, J., McGill, S., Sabot, D., Peach, M., & Raynor, D. (2020) · IBRO Reports · doi:10.1016/j.ibror.2020.10.006 · Cited by 53 · see citing works
The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation
Radley, J. J., Anderson, R. M., Cosme, C. V., Glanz, R. M., Miller, M. C., Romig‐Martin, S. A., & LaLumiere, R. T. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4961-14.2015 · Cited by 52 · see citing works
Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory
Anderson, R. M., Birnie, A. K., Koblesky, N. K., Romig‐Martin, S. A., & Radley, J. J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1385-14.2014 · Cited by 51 · see citing works
Where Have I Been? Where Should I Go? Spatial Working Memory on a Radial Arm Maze in a Rat Model of Depression
Richter, S. H., Zeuch, B., Lankisch, K., Gass, P., Durstewitz, D., & Vollmayr, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062458 · Cited by 51 · see citing works
Targeting Prefrontal Cortical Systems for Drug Development: Potential Therapies for Cognitive Disorders
Arnsten, A. F. T., & Wang, M. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103617 · Cited by 50 · see citing works
Self-citation
Toward a limbic cortical inhibitory network: implications for hypothalamic-pituitary-adrenal responses following chronic stress
Radley, J. J. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00007 · Cited by 47 · see citing works
Enhanced Hypothalamic NMDA Receptor Activity Contributes to Hyperactivity of HPA Axis in Chronic Stress in Male Rats
Zhou, J., Gao, Y., Zhang, X., Kosten, T. A., & Li, D. (2018) · Endocrinology · doi:10.1210/en.2017-03176 · Cited by 47 · see citing works
Pharmacological rescue of cognitive function in a mouse model of chemobrain
Nguyen, L. D., Fischer, T. T., & Ehrlich, B. E. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00463-2 · Cited by 45 · see citing works
Increased Risk Taking in Relation to Chronic Stress in Adults
Ceccato, S., Kudielka, B. M., & Schwieren, C. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.02036 · Cited by 45 · see citing works
The association between latent trauma and brain structure in children
Jeong, H. J., Durham, E. L., Moore, T. M., Dupont, R. M., McDowell, M. G., Cardenas‐Iniguez, C., Micciche, E. T., Berman, M. G., Lahey, B. B., & Kaczkurkin, A. N. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01357-z · Cited by 44 · see citing works
An Update on Protein Kinases as Therapeutic Targets—Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases
Silnitsky, S., Rubin, S. J. S., Zerihun, M., & Qvit, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417600 · Cited by 40 · see citing works
Chronic stress modulation of prefrontal cortical NMDA receptor expression disrupts limbic structure-prefrontal cortex interaction
Lee, Y., & Goto, Y. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07750.x · Cited by 42 · see citing works
Stress-induced alterations in prefrontal dendritic spines: Implications for post-traumatic stress disorder
Moench, K. M., & Wellman, C. L. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.12.035 · Cited by 41 · see citing works
ZiBuPiYin Recipe Protects db/db Mice from Diabetes-Associated Cognitive Decline through Improving Multiple Pathological Changes
Chen, J., Liang, L., Zhan, L., Zhou, Y., Zheng, L., Sun, X., Gong, J., Sui, H. X., Jiang, R., Zhang, F.-L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091680 · Cited by 40 · see citing works
The influence of stress and gonadal hormones on neuronal structure and function
Farrell, M. R., Gruene, T. M., & Shansky, R. M. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.03.003 · Cited by 39 · see citing works
Stress-Induced Impairment of a Working Memory Task: Role of Spiking Rate and Spiking History Predicted Discharge
Devilbiss, D. M., Jenison, R. L., & Berridge, C. W. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002681 · Cited by 39 · see citing works
Noradrenergic arousal after encoding reverses the course of systems consolidation in humans
Krenz, V., Sommer, T., Alink, A., Roozendaal, B., & Schwabe, L. (2021) · Nature Communications · doi:10.1038/s41467-021-26250-7 · Cited by 39 · see citing works
Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex
Yang, S., Wang, M., Paspalas, C. D., Crimins, J. L., Altman, M. T., Mazer, J. A., & Arnsten, A. F. T. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx357 · Cited by 38 · see citing works
Self-citation
Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro through a p53-dependent mitochondrial pathway
Zhang, X., Liu, X., Shang, H., Xu, Y., & Qian, M. (2011) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmr072 · Cited by 36 · see citing works
Unique Molecular Regulation of Higher-Order Prefrontal Cortical Circuits: Insights into the Neurobiology of Schizophrenia
Datta, D., & Arnsten, A. F. T. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00505 · Cited by 36 · see citing works
Self-citation
Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia
Arnsten, A. F. T., Woo, E., Yang, S., Wang, M., & Datta, D. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.003 · Cited by 35 · see citing works
Self-citation
Evidence for Similar Prefrontal Structural and Functional Alterations in Male and Female Rats Following Chronic Stress or Glucocorticoid Exposure
Anderson, R. M., Johnson, S. B., Lingg, R. T., Hinz, D. C., Romig‐Martin, S. A., & Radley, J. J. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz092 · Cited by 34 · see citing works
A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?
Abrial, E., Lucas, G., Scarna, H., Haddjeri, N., & Lambás‐Señas, L. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8210-4 · Cited by 34 · see citing works
Chronic Social Defeat Stress Modulates Dendritic Spines Structural Plasticity in Adult Mouse Frontal Association Cortex
Shu, Y., & Xu, T. (2017) · Neural Plasticity · doi:10.1155/2017/6207873 · Cited by 34 · see citing works
Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive decline
Kauser, H., Sahu, S., Kumar, S., & Panjwani, U. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.023 · Cited by 33 · see citing works
Stress induces microglia-associated synaptic circuit alterations in the dorsomedial prefrontal cortex
Liu, T., Lu, J., Łukasiewicz, K., Pan, B., & Zuo, Y. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100342 · Cited by 32 · see citing works
Chronic stress induces significant gene expression changes in the prefrontal cortex alongside alterations in adult hippocampal neurogenesis
Musaelyan, K., Yildizoglu, S., Bozeman, J., Preez, A. D., Egeland, M. T., Zunszain, P. A., Pariante, C. M., Fernandes, C., & Thuret, S. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa153 · Cited by 31 · see citing works
Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression
Lima‐Filho, R. A. S., Fortuna, J. T. S., Cozachenco, D., Isaac, A. R., Silva, N. M. L. E., Saldanha, A., Santos, L. E., Ferreira, S. T., Lourenco, M. V., & Felice, F. G. D. (2023) · eNeuro · doi:10.1523/eneuro.0256-22.2023 · Cited by 31 · see citing works
Preclinical studies of stress, extinction, and prefrontal cortex: intriguing leads and pressing questions
Wellman, C. L., & Moench, K. M. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5023-4 · Cited by 31 · see citing works
Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur, Y. S., Bentham, M. P., Zhou, W., Plantenga, M. E., McKee, S. A., & Picciotto, M. R. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4001-3 · Cited by 31 · see citing works
Effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats subjected to immobilization stress
Seo, M. K., Lee, C. H., Cho, H. Y., You, Y. S., Lee, B. J., Lee, J. G., Park, S. W., & Kim, Y. H. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.05.098 · Cited by 30 · see citing works
Dorsal-ventral distinction of chronic stress-induced electrophysiological alterations in the rat medial prefrontal cortex
Lee, Y. A., Poirier, P., Otani, S., & Goto, Y. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.039 · Cited by 30 · see citing works
Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain
Manukhina, E. B., Цейликман, В. Э., Karpenko, M. N., Pestereva, N. S., Tseilikman, O. B., Komelkova, M. V., Kondashevskaya, М. V., Goryacheva, A. V., Lapshin, M. S., Платковский, П. О., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21010345 · Cited by 29 · see citing works
Stress-induced impairments in prefrontal-mediated behaviors and the role of the N-methyl-d-aspartate receptor
Graybeal, C., Kiselycznyk, C., & Holmes, A. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.042 · Cited by 29 · see citing works
(Micro)Glia as Effectors of Cortical Volume Loss in Schizophrenia
Mallya, A. P., & Deutch, A. Y. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby088 · Cited by 29 · see citing works
Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish
Opler, L. A., Opler, M. G. A., & Arnsten, A. F. T. (2016) · CNS Spectrums · doi:10.1017/s1092852914000686 · Cited by 28 · see citing works
Self-citation

A role for PKC in mediating stress-induced prefrontal cortical structural plasticity and cognitive function
Chen, G., Henter, I. D., & Manji, H. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909771106 · Cited by 10 · see citing works
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Woo, E., Sansing, L. H., Arnsten, A. F. T., & Datta, D. (2021) · Chronic Stress · doi:10.1177/24705470211029254 · Cited by 159 · see citing works
Self-citation
Protein kinase C overactivity impairs prefrontal cortical regulation of working memory
Birnbaum, S. G., Yuan, P. X., Wang, M., Vijayraghavan, S., Bloom, A. K., Davis, D. J., Gobeske, K. T., Sweatt, J. D., Manji, H. K., & Arnsten, A. F. T. (2004) · Science · doi:10.1126/science.1100021 · Cited by 318 · see citing works
Self-citation
Stress Interferes with Working Memory
(2004) · Science s STKE · doi:10.1126/stke.2572004tw396
Chronic stimulation of alpha-2A-adrenoceptors with guanfacine protects rodent prefrontal cortex dendritic spines and cognition from the effects of chronic stress
Hains, A. B., Yabe, Y., & Arnsten, A. F. T. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.01.001 · Cited by 70 · see citing works
Self-citation

Authors: Hains, A. B., Vu, M. A. T., Maciejewski, P. K., van Dyck, C. H., Gottron, M., & Arnsten, A. F. T.
Affiliations: Yale University (US)
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street SHM C-303, New Haven, CT 06510; and
Corresponding author: Arnsten, Amy F. T.
ORCID: Vu, Mai Anh T.
Maciejewski, Paul K.
Arnsten, Amy F. T.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-10-20
Volume: 106
Issue: 42
Pages: 17957-17962
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0908563106
PMC: PMC2742406
OpenAlex: W1996838710
Cited by: 234
References: 66
Citations by year: 2026: 4 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 15 · 2021: 23 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 19 · 2016: 14 · 2015: 20 · 2014: 15 · 2013: 17 · 2012: 12
FWCI: 5.82
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
U.S. Public Health Service
National Institute on Alcohol Abuse and Alcoholism (RL1AA017536)
National Institute on Aging (R37AG006036)
National Institute of Mental Health (P50MH068789)
National Institute of Neurological Disorders and Stroke (K25NS044316)
National Center for Research Resources (U54RR024350)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: protein kinase C, chronic stress, dendritic spines, prefrontal cortex, working memory, chelerythrine, prelimbic cortex, pyramidal neurons, spine loss, neuroprotection, cognitive impairment, bipolar disorder, schizophrenia, post-traumatic stress disorder, lead poisoning
MeSH terms: Animals, Atrophy, Cognition, Disease Models, Animal, Humans, Male, Memory, Models, Neurological, Protein Kinase C, Stress, Physiological, Stress, Psychological, Signal Transduction, Rats, Sprague-Dawley, Prefrontal Cortex, Protein Kinase Inhibitors, Dendritic Spines, Rats, Benzophenanthridines

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

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks