30 results on '"Krugers, H.J."'
Search Results
2. List of Contributors
- Author
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Aguilera, G., primary, Allen, A.M., additional, Anacker, C., additional, Antoni, F.A., additional, Bader, M., additional, Baltatu, O.C., additional, Bartlang, M.S., additional, Bassi, J.K., additional, Bauer, C.M., additional, Beck, K., additional, Berridge, C.W., additional, Boari, B., additional, Borniger, J.C., additional, Bowers, M.E., additional, Bowman, R., additional, Buckingham, J.C., additional, Campos, L.A., additional, Carvalho, L.A., additional, Chen, A., additional, Cisse, Y.M., additional, Connelly, A.A., additional, de Bruijn, R., additional, de Jong, F.H., additional, de Kloet, E.R., additional, den Boon, F.S., additional, Fink, G., additional, Flory, J.D., additional, Flower, R.J., additional, Fong, A.Y., additional, Funder, J.W., additional, Gomez, J., additional, Gong, H., additional, Goonan, K., additional, Grigoriadis, D.E., additional, Handa, R.J., additional, Hassell Jr., J.E., additional, Hodges, T.E., additional, Hofland, J., additional, Holschbach, M.A., additional, Issler, O., additional, Jiang, C.-L., additional, Joëls, M., additional, Johnson, P.L., additional, Johnson, S.B., additional, Karst, H., additional, Khan, A.M., additional, Korosi, A., additional, Krugers, H.J., additional, Kyrou, I., additional, Lattin, C.R., additional, Lightman, S.L., additional, Liu, L., additional, Lovejoy, D.A., additional, Lowry, C.A., additional, Lucassen, P.J., additional, Luine, V., additional, Lundkvist, G.B., additional, Manfredini, F., additional, Manfredini, R., additional, Martin, L.B., additional, McCormick, C.M., additional, Meijer, O.C., additional, Menuet, C., additional, Michalec, O.M., additional, Mishra, N., additional, Nelson, R.J., additional, Nikkheslat, N., additional, Oomen, C.A., additional, Ortiz Zacarias, N.V., additional, Pariante, C.M., additional, Paul, E.D., additional, Pooley, J., additional, Price, L.H., additional, Pruessner, J.C., additional, Radley, J.J., additional, Randeva, H.S., additional, Rhodes, M.E., additional, Ridout, K.K., additional, Ridout, S.J., additional, Romero, L.M., additional, Roy, A., additional, Roy, R.N., additional, Russell, G., additional, Salmi, R., additional, Sarabdjitsingh, R.A., additional, Sarkar, D.K., additional, Sawchenko, P.E., additional, Schaaf, M.J.M., additional, Seckl, J.R., additional, Sevigny, C.P., additional, Shekhar, A., additional, Soreq, H., additional, Spencer, R.C., additional, Spiga, F., additional, Stoney, C.M., additional, Tiseo, R., additional, Tsigos, C., additional, Tyrka, A.R., additional, Walker, E.M., additional, Watts, A.G., additional, Wolf, O.T., additional, Yamashita, P.S.M., additional, Yehuda, R., additional, Zangrossi Jr., H., additional, Zorrilla, E.P., additional, and Zunszain, P.A., additional
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- 2017
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3. Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation
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Buurstede, J.C., Umeoka, E.H.L., Silva, M.S. da, Krugers, H.J., Joels, M., Meijer, O.C., SILS Other Research (FNWI), and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
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Pharmacology ,STRESS ,Pharmacological transcriptome filter ,Glucocorticoid receptor ,FEAR ,Hippocampus ,Cellular and Molecular Neuroscience ,Mice ,Receptors, Glucocorticoid ,Memory ,Animals ,BRAIN ,PLASTICITY ,Transcriptome ,Glucocorticoids ,ANTAGONIST ,Memory Consolidation - Abstract
Glucocorticoids regulate memory consolidation, facilitating long-term storage of relevant information to adequately respond to future stressors in similar conditions. This effect of glucocorticoids is well-established and is observed in multiple types of behaviour that depend on various brain regions. By and large, higher glucocorticoid levels strengthen event-related memory, while inhibition of glucocorticoid signalling impairs consolidation. The mechanism underlying this glucocorticoid effect remains unclear, but it likely involves the transcriptional effects of the glucocorticoid receptor (GR). We here used a powerful paradigm to investigate the transcriptional effects of GR in the dorsal hippocampus of mice after training in an auditory fear conditioning task, aiming to identify a shortlist of GR target genes associated to memory consolidation. Therefore, we utilized in an explorative study the properties of selective GR modulators (CORT108297 and CORT118335), alongside the endogenous agonist corticosterone and the classical GR antagonist RU486, to pinpoint GR-dependent transcriptional changes. First, we confirmed that glucocorticoids can modulate memory strength via GR activation. Subsequently, by assessing the specific effects of the available GR-ligands on memory strength, we established a pharmacological filter which we imposed on the hippocampal transcriptome data. This identified a manageable shortlist of eight genes by which glucocorticoids may modulate memory consolidation, warranting in-depth follow-up. Overall, we showcase the strength of the concept of pharmacological transcriptome filtering, which can be readily applied to other research topics with an established role of glucocorticoids.
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- 2022
4. How the COVID-19 pandemic highlights the necessity of animal research
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Genzel, L., Adan, R., Berns, A., Beucken, J.J.J.P van den, Blokland, A., Boddeke, E., Bogers, W.M., Bontrop, R., Bulthuis, R., Bousema, T., Clevers, H., Coenen, T., Dam, A.V., Deen, P.M.T., Dijk, K.W. van, Eggen, B.J.L., Elgersma, Y., Erdogan, I., Englitz, B., Fentener van Vlissingen, J.M., Fleur, S. la, Fouchier, R., Fitzsimons, C.P., Frieling, W., Haagmans, B., Heesters, B.A., Henckens, M.J.A.G., Herfst, S., Hol, E., Hove, D. van den, Jonge, M.I. de, Jonkers, J., Joosten, L.A.B., Kalsbeek, A., Kamermans, M., Kampinga, H.H., Kas, M.J., Keijer, J., Kersten, Sander, Kiliaan, A.J., Kooij, T.W., Kooijman, S., Koopman, W.J.H., Korosi, A., Krugers, H.J., Kuiken, T., Kushner, S.A., Langermans, J.A., Lesscher, H., Lucassen, P.J., Lutgens, E., Netea, M.G., Noldus, L.P.J.J., Meer, J.W.M. van der, Meye, F.J., Mul, J.D., Oers, K. van, Olivier, J.D., Pasterkamp, R.J., Philippens, I., Prickaerts, J., Pullox, B.J.A., Rensen, P.C., Rheenen, J. van, Rij, R.P. van, Ritsma, L., Rockx, B.H.G., Roozendaal, B., Schothorst, E.M. van, Stittelaar, K., Stockhofe, N., Swaab, D.F., Swart, R.L. de, Vanderschuren, L., Vries, T. de, Vrij, F. de, Wezel, R.J.A. van, Wierenga, C.J., Wiesmann, M., Willuhn, I., Zeeuw, C.I. de, Homberg, J.R., Genzel, L., Adan, R., Berns, A., Beucken, J.J.J.P van den, Blokland, A., Boddeke, E., Bogers, W.M., Bontrop, R., Bulthuis, R., Bousema, T., Clevers, H., Coenen, T., Dam, A.V., Deen, P.M.T., Dijk, K.W. van, Eggen, B.J.L., Elgersma, Y., Erdogan, I., Englitz, B., Fentener van Vlissingen, J.M., Fleur, S. la, Fouchier, R., Fitzsimons, C.P., Frieling, W., Haagmans, B., Heesters, B.A., Henckens, M.J.A.G., Herfst, S., Hol, E., Hove, D. van den, Jonge, M.I. de, Jonkers, J., Joosten, L.A.B., Kalsbeek, A., Kamermans, M., Kampinga, H.H., Kas, M.J., Keijer, J., Kersten, Sander, Kiliaan, A.J., Kooij, T.W., Kooijman, S., Koopman, W.J.H., Korosi, A., Krugers, H.J., Kuiken, T., Kushner, S.A., Langermans, J.A., Lesscher, H., Lucassen, P.J., Lutgens, E., Netea, M.G., Noldus, L.P.J.J., Meer, J.W.M. van der, Meye, F.J., Mul, J.D., Oers, K. van, Olivier, J.D., Pasterkamp, R.J., Philippens, I., Prickaerts, J., Pullox, B.J.A., Rensen, P.C., Rheenen, J. van, Rij, R.P. van, Ritsma, L., Rockx, B.H.G., Roozendaal, B., Schothorst, E.M. van, Stittelaar, K., Stockhofe, N., Swaab, D.F., Swart, R.L. de, Vanderschuren, L., Vries, T. de, Vrij, F. de, Wezel, R.J.A. van, Wierenga, C.J., Wiesmann, M., Willuhn, I., Zeeuw, C.I. de, and Homberg, J.R.
- Abstract
Contains fulltext : 225123.pdf (publisher's version ) (Closed access), Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future. This trend has led first and foremost to a substantial increase in the administrative burden and hurdles required to make timely advances in research and treatments for human and animal diseases. The current COVID-19 pandemic clearly highlights how much we actually rely on animal research. COVID-19 affects several organs and systems, and the various animal-free alternatives currently available do not come close to this complexity. In this Essay, we therefore argue that the use of animals is essential for the advancement of human and veterinary health.
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- 2020
5. Corticosteroid Actions on Electrical Activity in the Limbic Brain
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Joëls, M., primary, Karst, H., additional, Krugers, H.J., additional, and De Kloet, R., additional
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- 2009
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6. Early life stress impairs fear conditioning memory and synaptic plasticity; a potential role for GluN2B
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Lesuis, S.L., Lucassen, P.J., Krugers, H.J., and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
- Abstract
Programming of the brain by early life stress has been associated with alterations in structure and function of the dorsal hippocampus. Yet, the underlying molecular mechanisms remain largely elusive. In this study, we examined the effects of early life stress (ELS) - by housing mouse dams with limited nesting and bedding material from postnatal days 2-9 and examined in 6 month old offspring; 1) auditory fear conditioning, 2) expression of the hippocampal N-methyl-d-aspartate receptor (NMDA-R) subunits 2A and 2B (GluN2A, GluN2B), and expression of PSD-95 and synaptophysin, and 3) short- and long-term (LTP) synaptic plasticity. Given its critical role in NMDA receptor function and synaptic plasticity, we further examined the role of GluN2B in effects of ELS on synaptic plasticity and fear memory formation. We demonstrate that ELS impaired fear memory in 6 month old mice and decreased hippocampal LTP as well as the paired-pulse ratio (PPR). ELS also reduced hippocampal GluN2B expression. Interestingly, pharmacological blockade of GluN2B with the selective antagonist Ro25 6981 was less effective to reduce synaptic plasticity in ELS mice, and was also ineffective to impair memory retrieval in ELS mice. These studies suggest that ELS reduces hippocampal synaptic plasticity and fear memory formation and hampers GluN2B receptor function. As such, GluN2B may provide an important target for future strategies to prevent lasting ELS effects on cognition.
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- 2019
7. Chapter 13 - Early Life Stress- and Sex-Dependent Effects on Hippocampal Neurogenesis
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Lucassen, P.J., Korosi, A., Krugers, H.J., and Oomen, C.A.
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- 2017
- Full Text
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8. Early life stress- and sex-dependent effects on hippocampal neurogenesis
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Lucassen, P.J., Korosi, A., Krugers, H.J., Oomen, C.A., Fink, G., and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
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0301 basic medicine ,Neurogenesis ,Hippocampus ,Cognition ,Hippocampal formation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Mood ,medicine ,Anxiety ,medicine.symptom ,Psychology ,Neuroscience ,030217 neurology & neurosurgery ,Psychopathology ,Hormone - Abstract
Neurogenesis refers to the birth of new neurons in an adult brain, a form of structural plasticity that has been implicated in cognition, mood, and anxiety, and is well regulated by environmental and hormonal factors. Exposure to stress (hormones) generally inhibits neurogenesis. Here, we discuss (sex-dependent) effects of stress on adult hippocampal neurogenesis, and focus on stress during the sensitive period of early life. While the effects of acute, mild stress are generally short-lasting and recover quickly, chronic or severe forms of stress can induce longer-lasting reductions in adult neurogenesis, especially when encountered during early life. Some of these inhibitory effects of early stress can normalize after appropriate recovery periods, exercise, drugs targeting the stress system, and some antidepressants. Early life stress may (re-)program hippocampal plasticity, thereby altering the overall composition of the hippocampal circuit. This may modify stress responsivity, hippocampal function, later cognition, and the risk for psychopathology.
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- 2017
9. Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor
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Vogel, S., Klumpers, F., Navarro Schröder, T., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joëls, M., Doeller, C.F., Fernandez, G.S.E., Vogel, S., Klumpers, F., Navarro Schröder, T., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joëls, M., Doeller, C.F., and Fernandez, G.S.E.
- Abstract
Contains fulltext : 169192.pdf (publisher's version ) (Closed access), Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.
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- 2017
10. Interactions between N -Ethylmaleimide-sensitive factor and GluA2 contribute to effects of glucocorticoid hormones on AMPA receptor function in the rodent hippocampus
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Xiong, H., Cassé, F., Zhou, M., Xiong, Z.Q., Joels, M., Martin, S., Krugers, H.J., University of Amsterdam [Amsterdam] (UvA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Chinese Academy of Sciences [Shanghai], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Martin, Stephane, and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
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[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Hippocampus ,Synaptic Transmission ,stress ,Journal Article ,Animals ,Receptors, AMPA ,AMPA receptor ,Rats, Wistar ,NSF ,Glucocorticoids ,N-Ethylmaleimide-Sensitive Proteins ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Cells, Cultured ,AP2 ,Neurons ,musculoskeletal, neural, and ocular physiology ,[SCCO.NEUR]Cognitive science/Neuroscience ,Cell Membrane ,[SCCO.NEUR] Cognitive science/Neuroscience ,Hydrogen-Ion Concentration ,Immunohistochemistry ,Microscopy, Fluorescence ,nervous system ,synapses ,Corticosterone ,Fluorescence Recovery After Photobleaching - Abstract
Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptor (AMPAR) availability in the synapse, which is important for synaptic plasticity and memory formation. Peptides which specifically block the interaction between N-Ethylmaleimide-Sensitive Factor (NSF) and the AMPAR-subunit GluA2 prevented the increase in synaptic transmission and surface expression of AMPARs known to occur after corticosterone application to hippocampal neurons. Combining a live imaging Fluorescence Recovery After Photobleaching (FRAP) approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that this NSF/GluA2 interaction was also essential for the increase of the mobile fraction and reduction of the diffusion of AMPARs after treating hippocampal neurons with corticosterone. We conclude that the interaction between NSF and GluA2 contributes to the effects of corticosterone on AMPAR function. This article is protected by copyright. All rights reserved.
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- 2016
11. Within-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats
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van Hasselt, F.N., Tieskens, J.M., Trezza, V., Krugers, H.J., Vanderschuren, L.J.M.J., Joels, M., Emotion and Cognition, Dep of Animals in Science and Society, Structural and Functional Plasticity of the nervous system (SILS, FNWI), van Hasselt, F. N., Tieskens, J. M., Trezza, Viviana, Krugers, H. J., Vanderschuren, L. J. M. J., Joëls, M., Emotion and Cognition, and Dep of Animals in Science and Society
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Male ,Litter (animal) ,Offspring ,Experimental and Cognitive Psychology ,Medical sciences ,Affect (psychology) ,Developmental psychology ,Behavioral Neuroscience ,Reward ,Taverne ,Cognitive development ,Animals ,Rats, Long-Evans ,Bescherming en bevordering van de menselijke gezondheid ,Geneeskunde(GENK) ,Maternal Behavior ,Social Behavior ,Econometric and Statistical Methods: General ,Environmental enrichment ,Geneeskunde (GENK) ,Social change ,General [Econometric and Statistical Methods] ,Grooming ,Social relation ,Play and Playthings ,Rats ,Animals, Newborn ,Female ,Licking ,Psychology - Abstract
Maternal care represents an essential environmental factor during the first post-natal week(s) of rodents and is known to have lasting consequences for neuronal structure, brain function as well as behavioral outcome later in life, including social functions and reward-related processes. Previous experiments have shown that the amount of maternal care received by individual pups varies substantially, even within one litter. During adolescence, mammals display high levels of social play behavior, a rewarding form of social interaction that is of great importance for social and cognitive development. In order to investigate how maternal care influences adaptive social behavior later in life, we here examined whether individual differences in maternal licking and grooming (%LG) received during the first postnatal week affect social play behavior during adolescence. We observed that %LG received by male rats early in life correlates positively with the frequency and duration of pouncing and pinning, the two most characteristic behavioral expressions of social play behavior in rats. The latency to engage in social exploration also correlated with %LG. In female rats we observed no correlation between %LG and any social parameter. The data indicate that subtle variations in maternal care received early in life influence social interactions in male adolescent rats. These changes in social play likely have repercussions for the social development of male rats, suggesting that maternal care can have both direct and indirect effects on the behavioral development of the offspring.
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- 2012
12. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress
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Arp, J.M., Horst, J.P. ter, Loi, M., Blaauwen, J. den, Bangert, E., Fernandez, G.S.E., Joels, M., Oitzl, M.S., Krugers, H.J., Arp, J.M., Horst, J.P. ter, Loi, M., Blaauwen, J. den, Bangert, E., Fernandez, G.S.E., Joels, M., Oitzl, M.S., and Krugers, H.J.
- Abstract
Contains fulltext : 168332.pdf (publisher's version ) (Closed access), Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9 - affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence.
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- 2016
13. A stress-induced shift from trace to delay conditioning depends on the mineralocorticoid receptor
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Vogel, S., Klumpers, F., Kroes, M.C.W., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joels, M., Fernandez, G.S.E., Vogel, S., Klumpers, F., Kroes, M.C.W., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joels, M., and Fernandez, G.S.E.
- Abstract
Contains fulltext : 152028.pdf (publisher's version ) (Closed access), BACKGROUND: Fear learning in stressful situations is highly adaptive for survival by steering behavior in subsequent situations, but fear learning can become disproportionate in vulnerable individuals. Despite the potential clinical significance, the mechanism by which stress modulates fear learning is poorly understood. Memory theories state that stress can cause a shift away from more controlled processing depending on the hippocampus toward more reflexive processing supported by the amygdala and striatum. This shift may be mediated by activation of the mineralocorticoid receptor (MR) for cortisol. We investigated how stress shifts processes underlying cognitively demanding learning versus less demanding fear learning using a combined trace and delay fear conditioning paradigm. METHODS: In a pharmacological functional magnetic resonance imaging study, we tested 101 healthy men probing the effects of stress (socially evaluated cold pressor vs. control procedure) and MR-availability (400 mg spironolactone vs. placebo) in a randomized, placebo-controlled, full-factorial, between-subjects design. RESULTS: Effective stress induction and successful conditioning were confirmed by subjective, physiologic, and somatic data. In line with a stress-induced shift, stress enhanced later recall of delay compared with trace conditioning in the MR-available groups as indexed by skin conductance responses. During learning, this was accompanied by a stress-induced reduction of learning-related hippocampal activity for trace conditioning. The stress-induced shift in fear and neural processing was absent in the MR-blocked groups. CONCLUSIONS: Our results are in line with a stress-induced shift in fear learning, mediated by the MR, resulting in a dominance of cognitively less demanding amygdala-based learning, which might be particularly prominent in individuals with high MR sensitivity.
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- 2015
14. A stress-induced shift in spatial memory systems depends on the availability of the mineralocorticoid receptor in humans
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Vogel, S., Klumpers, F., Navarro Schröder, T., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joëls, M., Döller, C.F.A., Fernandez, G.S.E., Vogel, S., Klumpers, F., Navarro Schröder, T., Oplaat, K.T., Krugers, H.J., Oitzl, M.S., Joëls, M., Döller, C.F.A., and Fernandez, G.S.E.
- Abstract
Contains fulltext : 168883.pdf (publisher's version ) (Closed access)
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- 2015
15. Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum
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Vogel, S., Klumpers, F., Krugers, H.J., Fang, Z., Oplaat, K.T., Oitzl, M.S., Joels, M., Fernandez, G.S.E., Vogel, S., Klumpers, F., Krugers, H.J., Fang, Z., Oplaat, K.T., Oitzl, M.S., Joels, M., and Fernandez, G.S.E.
- Abstract
Contains fulltext : 154656.pdf (publisher's version ) (Closed access), Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol.
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- 2015
16. Maternal care received by individual pups correlates with adult CA1 dendritic morphology and synaptic plasticity in a sex-dependent manner
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van Hasselt, F.N., Boudewijns, Z.S., Knaap, N.J.F. van der, Krugers, H.J., Joëls, M., and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
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DCN MP - Plasticity and memory - Abstract
Item does not contain fulltext Maternal care is an important environmental factor for rats early in life. Adult offspring from dams exhibiting extremely high versus low maternal care differ remarkably in dendritic complexity and long-term synaptic potentiation in the CA1 area. However, >70% of the pups do not belong to these extreme categories of maternal care, questioning the general relevance of these observations. Therefore, the present study investigated whether the influence of maternal care is discernable over its entire range and can serve as an index predicting later CA1 structure and function. The amount of licking and grooming (%LG) received was determined for each pup during the first postnatal week. In males, both total apical branch length and dendritic complexity correlated significantly and positively with %LG. In females, we observed a nonsignificant negative correlation, also when controlled for variations in oestradiol and progesterone levels. The correlation in females was significantly different from that in males. No significant correlation was observed between the %LG and the amount of synaptic potentiation, either in male or in female offspring, regardless of whether slices had been treated with corticosterone or vehicle. However, in male rats, the degree of potentiation seen after corticosterone compared to vehicle treatment was almost significantly related to the %LG received early in life; this differed significantly from that observed in females. The data from the present study suggest that %LG received early in life results in mild, yet sex-dependent effects on adult CA1 structure and function.
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- 2012
17. Mineralocorticoid receptors guide spatial and stimulus-response learning in mice
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Arp, J.M., Horst, J.P. ter, Kanatsou, S., Fernandez, G.S.E., Joëls, M., Krugers, H.J., Oitzl, M.S., Arp, J.M., Horst, J.P. ter, Kanatsou, S., Fernandez, G.S.E., Joëls, M., Krugers, H.J., and Oitzl, M.S.
- Abstract
Contains fulltext : 135491.pdf (publisher's version ) (Open Access), Adrenal corticosteroid hormones act via mineralocorticoid (MR) and glucocorticoid receptors (GR) in the brain, influencing learning and memory. MRs have been implicated in the initial behavioral response in novel situations, which includes behavioral strategies in learning tasks. Different strategies can be used to solve navigational tasks, for example hippocampus-dependent spatial or striatum-dependent stimulus-response strategies. Previous studies suggested that MRs are involved in spatial learning and induce a shift between learning strategies when animals are allowed a choice between both strategies. In the present study, we further explored the role of MRs in spatial and stimulus-response learning in two separate circular holeboard tasks using female mice with forebrain-specific MR deficiency and MR overexpression and their wildtype control littermates. In addition, we studied sex-specific effects using male and female MR-deficient mice. First, we found that MR-deficient compared to control littermates and MR-overexpressing mice display altered exploratory and searching behavior indicative of impaired acquisition of novel information. Second, female (but not male) MR-deficient mice were impaired in the spatial task, while MR-overexpressing female mice showed improved performance in the spatial task. Third, MR-deficient mice were also impaired in the stimulus-response task compared to controls and (in the case of females) MR-overexpressing mice. We conclude that MRs are important for coordinating the processing of information relevant for spatial as well as stimulus-response learning.
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- 2014
18. Corticosteroid Actions on Electrical Activity in the Limbic Brain
- Author
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Joëls, M., Karst, H., Krugers, H.J., de Kloet, R., Pfaff, D.W., Arnold, A.P., Etgen, A.M., Fahrbach, S.E., Rubin, R.T., and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
- Subjects
Amygdala ,chemistry.chemical_compound ,medicine.anatomical_structure ,Glucocorticoid receptor ,Mineralocorticoid receptor ,chemistry ,Corticosterone ,Synaptic plasticity ,medicine ,Chronic stress ,Receptor ,Psychology ,Neuroscience ,Hormone - Abstract
Corticosteroid hormones easily enter the brain and bind to receptors that translocate to the nucleus, where they regulate transcription of responsive genes. Within the brain corticosterone binds with high affinity to mineralocorticoid receptors (MRs) that have a restricted distribution. Glucocorticoid receptors (GRs), which are much more widespread, display a tenfold lower affinity. Principal cells in limbic structures contain gluco- as well as MRs. Electrophysiological studies over the past decades have addressed the role of these two receptor types in information transfer through limbic areas, most notably the hippocampus. The current view is that intracellular MRs serve to maintain steady electrical activity and optimal viability in neurons under nonstress conditions. Following stress exposure, rapid nongenomic effects via MRs in the plasma membrane are thought to enhance excitability, in concert with other stress hormones. This will promote the appraisal and most likely the first stages of encoding of the stressful situation. At the same time, GRs are activated which several hours later - through delayed genomic pathways - restore excitability and preserve earlier encoded information. While brief activation of GRs in the context of a stressful situation leads to adaptive responses, the pleiotropic hormone effects can become a vulnerability factor when the circuit is exposed to additional challenges, for example, during ischemia, or when GRs are repeatedly activated such as during chronic stress.
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- 2009
19. Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats
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van Hasselt, F.N., de Visser, L., Tieskens, J.M., Cornelisse, S., Baars, A.M., Lavrijsen, M., Krugers, H.J., van den Bos, R., Joëls, M., van Hasselt, F.N., de Visser, L., Tieskens, J.M., Cornelisse, S., Baars, A.M., Lavrijsen, M., Krugers, H.J., van den Bos, R., and Joëls, M.
- Abstract
Contains fulltext : 108331.pdf (publisher's version ) (Open Access), Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.
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- 2012
20. Within-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats
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Emotion and Cognition, Dep of Animals in Science and Society, van Hasselt, F.N., Tieskens, J.M., Trezza, V., Krugers, H.J., Vanderschuren, L.J.M.J., Joels, M., Emotion and Cognition, Dep of Animals in Science and Society, van Hasselt, F.N., Tieskens, J.M., Trezza, V., Krugers, H.J., Vanderschuren, L.J.M.J., and Joels, M.
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- 2012
21. Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity
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Martin, S. (Stéphane), Henley, J.M. (Jeremy), Holman, D. (David), Zhou, M. (Ming), Wiegert, O. (Olof), Spronsena, M. (Myrrhe) van, Joëls, M. (Marian), Hoogenraad, C.C. (Casper), Krugers, H.J. (Harmen), Martin, S. (Stéphane), Henley, J.M. (Jeremy), Holman, D. (David), Zhou, M. (Ming), Wiegert, O. (Olof), Spronsena, M. (Myrrhe) van, Joëls, M. (Marian), Hoogenraad, C.C. (Casper), and Krugers, H.J. (Harmen)
- Abstract
Background: The stress hormone corticosterone has the ability both to enhance and suppress synaptic plasticity and learning and memory processes. However, until today there is very little known about the molecular mechanism that underlies the bidirectional effects of stress and corticosteroid hormones on synaptic efficacy and learning and memory processes. In this study we investigate the relationship between corticosterone and AMPA receptors which play a critical role in activity-dependent plasticity and hippocampal-dependent learning. Methodology/Principal Findings: Using immunocytochemistry and live cell imaging techniques we show that corticosterone selectively increases surface expression of the AMPAR subunit GluR2 in primary hippocampal cultures via a glucocorticoid receptor and protein synthesis dependent mechanism. In agreement, we report that corticosterone also dramatically increases the fraction of surface expressed GluR2 that undergo lateral diffusion. Furthermore, our data indicate that corticosterone facilitates NMDAR-invoked endocytosis of both synaptic and extra-synaptic GluR2 under conditions that weaken synaptic transmission. Conclusion/Significance: Our results reveal that corticosterone increases mobile GluR2 containing AMPARs. The enhanced lateral diffusion properties can both facilitate the recruitment of AMPARs but under appropriate conditions facilitate the loss of synaptic AMPARs (LTD). These actions may underlie both the facilitating and suppressive effects of corticosteroid hormones on synaptic plasticity and learning and memory and suggest that these hormones accentuate synaptic efficacy.
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- 2009
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22. Stress and excitatory synapses: From health to disease
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Timmermans, W., primary, Xiong, H., additional, Hoogenraad, C.C., additional, and Krugers, H.J., additional
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- 2013
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23. Dissociation between apoptosis, neurogenesis, and synaptic potentiation in the dentate gyrus of adrenalectomized rats
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Krugers, H.J., primary, van der Linden, S., additional, van Olst, E., additional, Alfarez, D.N., additional, Maslam, S., additional, Lucassen, P.J., additional, and Joëls, M., additional
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- 2007
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24. Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals
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Alfarez, D.N., primary, Karst, H., additional, Velzing, E.H., additional, Joëls, M., additional, and Krugers, H.J., additional
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- 2007
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25. Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation
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Alfarez, D.N, primary, Wiegert, O, additional, Joëls, M, additional, and Krugers, H.J, additional
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- 2002
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26. Synthesis and organ distribution of [18F]fluoro-org 6141 in the rat: A potential glucocorticoid receptor ligand for positron emission tomography
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Visser, G.M., primary, Krugers, H.J., additional, Luurtsema, G., additional, van Waarde, A., additional, Elsinga, P.H., additional, DeKloet, E.R., additional, Groen, M.B., additional, Bohus, B., additional, Go, K.G., additional, Paans, A.M.J., additional, Korf, J., additional, and Vaalburg, W., additional
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- 1995
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27. The rat hippocampus as a target for prolonged stress: Biochemical and behavioral effects
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Krugers, H.J., primary and Korf, J., additional
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- 1995
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28. A single social stress-experience alters glutamate receptor-binding in rat hippocampal CA3 area
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Krugers, H.J., primary, Koolhaas, J.M., additional, Bohus, B., additional, and Korf, J., additional
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- 1993
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29. Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals.
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Alfarez, D.N., Karst, H., Velzing, E.H., Joëls, M., and Krugers, H.J.
- Abstract
Remodeling of synaptic networks is believed to contribute to synaptic plasticity and long-term memory performance, both of which are modulated by chronic stress. We here examined whether chronic stress modulates dendritic complexity of hippocampal CA1 pyramidal cells, under conditions of basal as well as elevated corticosteroid hormone levels. Slices were prepared from naïve, handled or chronically stressed animals and briefly treated with vehicle or corticosterone (100 nM); neurons were visualized with a fluorescent dye injected into individual CA1 pyramidal cells. We observed that 21 days of unpredictable stress did not affect hippocampal CA1 apical or basal dendritic morphology compared with naïve animals when corticosteroid levels were low. Only when slices from stressed animals were also exposed to elevated corticosteroid levels, a significant reduction in apical (but not basal) dendritic length became apparent. Unexpectedly, animals that were handled or 3 weeks showed a reduction in both apical dendritic length and number of apical branch points when compared with naïve animals. Apical dendritic length and number of branch points were restored to levels found in naïve animals several hours after in vitro treatment with 100 nM corticosterone. All effects of acute corticosterone administration could be prevented by the glucocorticoid receptor antagonist RU38486 given during the last 4 days of the stress or handling protocol. We conclude that brief exposure to high concentrations of corticosterone can differently affect apical dendritic structure, depending on the earlier history of the animal, a process that critically depends on involvement of the glucocorticoid receptor. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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30. The effect of theophylline and immobilization stress on haloperidol-induced catalepsy and on metabolism in the striatum and hippocampus, studied with lactography
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Dijk, S., Krugers, H.J., and Korf, J.
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- 1991
- Full Text
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