A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system

Lopes MW, Leal RB, Guarnieri R, Schwarzbold ML, Hoeller A, Diaz AP, Boos GL, Lin K, Linhares MN, Nunes JC, Quevedo J, et al. (2016)

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Lopes, M. W.; Leal, R. B.; Guarnieri, R.; Schwarzbold, M. L.; Hoeller, A.; Diaz, A. P.; Boos, G. L.; Lin, K.; Linhares, M. N.; Nunes, J. C.; Quevedo, J.; Bortolotto, Z. A.
Abstract / Bemerkung
Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.
Page URI


Lopes MW, Leal RB, Guarnieri R, et al. A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY. 2016;6(12): e986.
Lopes, M. W., Leal, R. B., Guarnieri, R., Schwarzbold, M. L., Hoeller, A., Diaz, A. P., Boos, G. L., et al. (2016). A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY, 6(12), e986. doi:10.1038/tp.2016.251
Lopes, M. W., Leal, R. B., Guarnieri, R., Schwarzbold, M. L., Hoeller, A., Diaz, A. P., Boos, G. L., Lin, K., Linhares, M. N., Nunes, J. C., et al. (2016). A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY 6:e986.
Lopes, M.W., et al., 2016. A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY, 6(12): e986.
M.W. Lopes, et al., “A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system”, TRANSLATIONAL PSYCHIATRY, vol. 6, 2016, : e986.
Lopes, M.W., Leal, R.B., Guarnieri, R., Schwarzbold, M.L., Hoeller, A., Diaz, A.P., Boos, G.L., Lin, K., Linhares, M.N., Nunes, J.C., Quevedo, J., Bortolotto, Z.A., Markowitsch, H.J., Lightman, S.L., Walz, R.: A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY. 6, : e986 (2016).
Lopes, M. W., Leal, R. B., Guarnieri, R., Schwarzbold, M. L., Hoeller, A., Diaz, A. P., Boos, G. L., Lin, K., Linhares, M. N., Nunes, J. C., Quevedo, J., Bortolotto, Z. A., Markowitsch, Hans J., Lightman, S. L., and Walz, R. “A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system”. TRANSLATIONAL PSYCHIATRY 6.12 (2016): e986.

4 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Amygdala levels of the GluA1 subunit of glutamate receptors and its phosphorylation state at serine 845 in the anterior hippocampus are biomarkers of ictal fear but not anxiety.
Leal RB, Lopes MW, Formolo DA, de Carvalho CR, Hoeller AA, Latini A, Sousa DS, Wolf P, Prediger RD, Bortolotto ZA, Linhares MN, Lin K, Walz R., Mol Psychiatry (), 2018
PMID: 29880883
Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.
Pauli C, Schwarzbold ML, Diaz AP, de Oliveira Thais MER, Kondageski C, Linhares MN, Guarnieri R, de Lemos Zingano B, Ben J, Nunes JC, Markowitsch HJ, Wolf P, Wiebe S, Lin K, Walz R., Epilepsia 58(5), 2017
PMID: 28332703
PCLO rs2522833-mediated gray matter volume reduction in patients with drug-naive, first-episode major depressive disorder.
Igata R, Katsuki A, Kakeda S, Watanabe K, Igata N, Hori H, Konishi Y, Atake K, Kawasaki Y, Korogi Y, Yoshimura R., Transl Psychiatry 7(5), 2017
PMID: 28556829
Mitochondrial respiratory chain complex enzyme activities of limbic structures and psychiatric diagnosis in temporal lobe epilepsy patients: Preliminary results.
Osório CM, Lin K, Guarnieri R, de Oliveira Thais MER, Dresch Vascouto H, Remor AP, Lopes MW, Linhares MN, Ben J, de Paula Martins R, Hoeller AA, Wolf P, Latini A, Walz R., CNS Neurosci Ther 23(8), 2017
PMID: 28656687

75 References

Daten bereitgestellt von Europe PubMed Central.

The influence of stress hormones on fear circuitry.
Rodrigues SM, LeDoux JE, Sapolsky RM., Annu. Rev. Neurosci. 32(), 2009
PMID: 19400714
The effects of stress on brain and adrenal stem cells.
Rubin de Celis MF, de Celis MF, Bornstein SR, Androutsellis-Theotokis A, Andoniadou CL, Licinio J, Wong ML, Ehrhart-Bornstein M., Mol. Psychiatry 21(5), 2016
PMID: 26809844
How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental Health Surveys.
Kessler RC, Rose S, Koenen KC, Karam EG, Stang PE, Stein DJ, Heeringa SG, Hill ED, Liberzon I, McLaughlin KA, McLean SA, Pennell BE, Petukhova M, Rosellini AJ, Ruscio AM, Shahly V, Shalev AY, Silove D, Zaslavsky AM, Angermeyer MC, Bromet EJ, de Almeida JM, de Girolamo G, de Jonge P, Demyttenaere K, Florescu SE, Gureje O, Haro JM, Hinkov H, Kawakami N, Kovess-Masfety V, Lee S, Medina-Mora ME, Murphy SD, Navarro-Mateu F, Piazza M, Posada-Villa J, Scott K, Torres Y, Carmen Viana M., World Psychiatry 13(3), 2014
PMID: 25273300
Stress and the brain: individual variability and the inverted-U.
Sapolsky RM., Nat. Neurosci. 18(10), 2015
PMID: 26404708
The stressed hippocampus, synaptic plasticity and lost memories.
Kim JJ, Diamond DM., Nat. Rev. Neurosci. 3(6), 2002
PMID: 12042880
Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy.
Mitra R, Sapolsky RM., Proc. Natl. Acad. Sci. U.S.A. 105(14), 2008
PMID: 18391224
Time-dependent effects of cortisol on selective attention and emotional interference: a functional MRI study.
Henckens MJ, van Wingen GA, Joels M, Fernandez G., Front Integr Neurosci 6(), 2012
PMID: 22973203
Time-dependent effects of corticosteroids on human amygdala processing.
Henckens MJ, van Wingen GA, Joels M, Fernandez G., J. Neurosci. 30(38), 2010
PMID: 20861377
Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.
Sapolsky RM., Arch. Gen. Psychiatry 57(10), 2000
PMID: 11015810
Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome.
Starkman MN, Gebarski SS, Berent S, Schteingart DE., Biol. Psychiatry 32(9), 1992
PMID: 1450290
Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.
Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, Schteingart DE., Biol. Psychiatry 46(12), 1999
PMID: 10624540
Cushing's syndrome: a psychiatric study of 29 patients.
Cohen SI., Br J Psychiatry 136(), 1980
PMID: 7370477
A synaptic basis for memory storage in the cerebral cortex.
Bear MF., Proc. Natl. Acad. Sci. U.S.A. 93(24), 1996
PMID: 8942956
Long-term depression in hippocampus.
Bear MF, Abraham WC., Annu. Rev. Neurosci. 19(), 1996
PMID: 8833450
Engineering a memory with LTD and LTP.
Nabavi S, Fox R, Proulx CD, Lin JY, Tsien RY, Malinow R., Nature 511(7509), 2014
PMID: 24896183
Synaptic plasticity and memory: an evaluation of the hypothesis.
Martin SJ, Grimwood PD, Morris RG., Annu. Rev. Neurosci. 23(), 2000
PMID: 10845078
A synaptic model of memory: long-term potentiation in the hippocampus.
Bliss TV, Collingridge GL., Nature 361(6407), 1993
PMID: 8421494
Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex.
Jerusalinsky D, Ferreira MB, Walz R, Da Silva RC, Bianchin M, Ruschel AC, Zanatta MS, Medina JH, Izquierdo I., Behav. Neural Biol. 58(1), 1992
PMID: 1417675
Memory processing by the limbic system: role of specific neurotransmitter systems.
Izquierdo I, Medina JH, Bianchin M, Walz R, Zanatta MS, Da Silva RC, Bueno e Silva M, Ruschel AC, Paczko N., Behav. Brain Res. 58(1-2), 1993
PMID: 7907882
Time-dependent impairment of inhibitory avoidance retention in rats by posttraining infusion of a mitogen-activated protein kinase kinase inhibitor into cortical and limbic structures.
Walz R, Roesler R, Quevedo J, Sant'Anna MK, Madruga M, Rodrigues C, Gottfried C, Medina JH, Izquierdo I., Neurobiol Learn Mem 73(1), 2000
PMID: 10686120
Learning induces long-term potentiation in the hippocampus.
Whitlock JR, Heynen AJ, Shuler MG, Bear MF., Science 313(5790), 2006
PMID: 16931756
Role of adrenal stress hormones in forming lasting memories in the brain.
McGaugh JL, Roozendaal B., Curr. Opin. Neurobiol. 12(2), 2002
PMID: 12015238
Involvement of stress-released corticotropin-releasing hormone in the basolateral amygdala in regulating memory consolidation.
Roozendaal B, Brunson KL, Holloway BL, McGaugh JL, Baram TZ., Proc. Natl. Acad. Sci. U.S.A. 99(21), 2002
PMID: 12361983
Synaptic AMPA receptor composition in development, plasticity and disease.
Henley JM, Wilkinson KA., Nat. Rev. Neurosci. 17(6), 2016
PMID: 27080385
AMPARs and synaptic plasticity: the last 25 years.
Huganir RL, Nicoll RA., Neuron 80(3), 2013
PMID: 24183021
Roles of subunit phosphorylation in regulating glutamate receptor function.
Wang JQ, Guo ML, Jin DZ, Xue B, Fibuch EE, Mao LM., Eur. J. Pharmacol. 728(), 2013
PMID: 24291102
Coordination of Protein Phosphorylation and Dephosphorylation in Synaptic Plasticity.
Woolfrey KM, Dell'Acqua ML., J. Biol. Chem. 290(48), 2015
PMID: 26453308
PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity.
Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R., Nat. Neurosci. 6(2), 2003
PMID: 12536214
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity.
Lee HK, Barbarosie M, Kameyama K, Bear MF, Huganir RL., Nature 405(6789), 2000
PMID: 10879537
Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression.
Tavalin SJ, Colledge M, Hell JW, Langeberg LK, Huganir RL, Scott JD., J. Neurosci. 22(8), 2002
PMID: 11943807
Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.
Lee HK, Takamiya K, Han JS, Man H, Kim CH, Rumbaugh G, Yu S, Ding L, He C, Petralia RS, Wenthold RJ, Gallagher M, Huganir RL., Cell 112(5), 2003
PMID: 12628184
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants.
Duman RS, Aghajanian GK, Sanacora G, Krystal JH., Nat. Med. 22(3), 2016
PMID: 26937618
Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus.
Whitehead G, Jo J, Hogg EL, Piers T, Kim DH, Seaton G, Seok H, Bru-Mercier G, Son GH, Regan P, Hildebrandt L, Waite E, Kim BC, Kerrigan TL, Kim K, Whitcomb DJ, Collingridge GL, Lightman SL, Cho K., Brain 136(Pt 12), 2013
PMID: 24271563
A randomized, controlled trial of surgery for temporal-lobe epilepsy.
Wiebe S, Blume WT, Girvin JP, Eliasziw M; Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group., N. Engl. J. Med. 345(5), 2001
PMID: 11484687
Volumetric evidence of bilateral damage in unilateral mesial temporal lobe epilepsy.
Araujo D, Santos AC, Velasco TR, Wichert-Ana L, Terra-Bustamante VC, Alexandre V Jr, Carlotti CG Jr, Assirati JA Jr, Machado HR, Walz R, Leite JP, Sakamoto AC., Epilepsia 47(8), 2006
PMID: 16922881
Do psychiatric comorbidities predict postoperative seizure outcome in temporal lobe epilepsy surgery?
Guarnieri R, Walz R, Hallak JE, Coimbra E, de Almeida E, Cescato MP, Velasco TR, Alexandre V Jr, Terra VC, Carlotti CG Jr, Assirati JA Jr, Sakamoto AC., Epilepsy Behav 14(3), 2009
PMID: 19186216
Hippocampal sclerosis and ipsilateral headache among mesial temporal lobe epilepsy patients.
Nunes JC, Zakon DB, Claudino LS, Guarnieri R, Bastos A, Queiroz LP, Walz R, Lin K., Seizure 20(6), 2011
PMID: 21439855
Predictors of quality of life in patients with refractory mesial temporal lobe epilepsy.
Pauli C, Thais ME, Claudino LS, Bicalho MA, Bastos AC, Guarnieri R, Nunes JC, Lin K, Linhares MN, Walz R., Epilepsy Behav 25(2), 2012
PMID: 23032134
Utility of ictal single photon emission computed tomography in mesial temporal lobe epilepsy with hippocampal atrophy: a randomized trial.
Velasco TR, Wichert-Ana L, Mathern GW, Araujo D, Walz R, Bianchin MM, Dalmagro CL, Leite JP, Santos AC, Assirati JA Jr, Carlotti CG Jr, Sakamoto AC., Neurosurgery 68(2), 2011
PMID: 21135733
Validation of diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy.
de Lemos Zingano B, Guarnieri R, Diaz AP, Schwarzbold ML, Bicalho MA, Claudino LS, Markowitsch HJ, Wolf P, Lin K, Walz R., Epilepsy Behav 50(), 2015
PMID: 26119622
Dexamethasone for intracranial neurosurgery and anaesthesia.
Hockey B, Leslie K, Williams D., J Clin Neurosci 16(11), 2009
PMID: 19665383

Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.
Ronsoni MF, Remor AP, Lopes MW, Hohl A, Troncoso IH, Leal RB, Boos GL, Kondageski C, Nunes JC, Linhares MN, Lin K, Latini AS, Walz R., Neurochem. Res. 41(4), 2015
PMID: 26586405
Differential Activation of Mitogen-Activated Protein Kinases, ERK 1/2, p38(MAPK) and JNK p54/p46 During Postnatal Development of Rat Hippocampus.
Costa AP, Lopes MW, Rieger DK, Barbosa SG, Goncalves FM, Xikota JC, Walz R, Leal RB., Neurochem. Res. 41(5), 2015
PMID: 26700434
Time course evaluation of behavioral impairments in the pilocarpine model of epilepsy.
Lopes MW, Lopes SC, Santos DB, Costa AP, Goncalves FM, de Mello N, Prediger RD, Farina M, Walz R, Leal RB., Epilepsy Behav 55(), 2016
PMID: 26773677
Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy.
Lopes MW, Soares FM, de Mello N, Nunes JC, Cajado AG, de Brito D, de Cordova FM, da Cunha RM, Walz R, Leal RB., Exp Brain Res 226(2), 2013
PMID: 23392471
Region-specific alterations of AMPA receptor phosphorylation and signaling pathways in the pilocarpine model of epilepsy.
Lopes MW, Lopes SC, Costa AP, Goncalves FM, Rieger DK, Peres TV, Eyng H, Prediger RD, Diaz AP, Nunes JC, Walz R, Leal RB., Neurochem. Int. 87(), 2015
PMID: 25983036
Time-dependent modulation of mitogen activated protein kinases and AKT in rat hippocampus and cortex in the pilocarpine model of epilepsy.
Lopes MW, Soares FM, de Mello N, Nunes JC, de Cordova FM, Walz R, Leal RB., Neurochem. Res. 37(9), 2012
PMID: 22614924
Effects of pentylenetetrazole kindling on mitogen-activated protein kinases levels in neocortex and hippocampus of mice.
Ben J, de Oliveira PA, Goncalves FM, Peres TV, Matheus FC, Hoeller AA, Leal RB, Walz R, Prediger RD., Neurochem. Res. 39(12), 2014
PMID: 25316496
CaMKII: a molecular substrate for synaptic plasticity and memory.
Shonesy BC, Jalan-Sakrikar N, Cavener VS, Colbran RJ., Prog Mol Biol Transl Sci 122(), 2014
PMID: 24484698
Emerging role of CaMKII in neuropsychiatric disease.
Robison AJ., Trends Neurosci. 37(11), 2014
PMID: 25087161
Stress responsiveness varies over the ultradian glucocorticoid cycle in a brain-region-specific manner.
Sarabdjitsingh RA, Conway-Campbell BL, Leggett JD, Waite EJ, Meijer OC, de Kloet ER, Lightman SL., Endocrinology 151(11), 2010
PMID: 20861228
Corticosteroid induced decoupling of the amygdala in men.
Henckens MJ, van Wingen GA, Joels M, Fernandez G., Cereb. Cortex 22(10), 2011
PMID: 22079927
Dynamic Regulation of AMPAR Phosphorylation In Vivo Following Acute Behavioral Stress.
Caudal D, Rame M, Jay TM, Godsil BP., Cell. Mol. Neurobiol. 36(8), 2016
PMID: 26814839
Metaplasticity of amygdalar responses to the stress hormone corticosterone.
Karst H, Berger S, Erdmann G, Schutz G, Joels M., Proc. Natl. Acad. Sci. U.S.A. 107(32), 2010
PMID: 20663957
Acute effects of hydrocortisone on the human brain: an fMRI study.
Lovallo WR, Robinson JL, Glahn DC, Fox PT., Psychoneuroendocrinology 35(1), 2010
PMID: 19836143

Amygdala, affect and cognition: evidence from 10 patients with Urbach-Wiethe disease.
Siebert M, Markowitsch HJ, Bartel P., Brain 126(Pt 12), 2003
PMID: 12937075
Amygdalar activation associated with positive and negative facial expressions.
Yang TT, Menon V, Eliez S, Blasey C, White CD, Reid AJ, Gotlib IH, Reiss AL., Neuroreport 13(14), 2002
PMID: 12395114
A circuit mechanism for differentiating positive and negative associations.
Namburi P, Beyeler A, Yorozu S, Calhoon GG, Halbert SA, Wichmann R, Holden SS, Mertens KL, Anahtar M, Felix-Ortiz AC, Wickersham IR, Gray JM, Tye KM., Nature 520(7549), 2015
PMID: 25925480
The amygdala and emotional memory.
Cahill L, Babinsky R, Markowitsch HJ, McGaugh JL., Nature 377(6547), 1995
PMID: 7566084
Polymorphisms in the GRIA1 gene region in psychotic bipolar disorder
Glutamate AMPA receptor subunit 1 gene (GRIA1) and DSM-IV-TR schizophrenia: A pilot case-control association study in an Italian sample
Stoichiometry and phosphoisotypes of hippocampal AMPA-type glutamate receptor phosphorylation.
Hosokawa T, Mitsushima D, Kaneko R, Hayashi Y., Neuron 85(1), 2014
PMID: 25533481
Extensive phosphorylation of AMPA receptors in neurons.
Diering GH, Heo S, Hussain NK, Liu B, Huganir RL., Proc. Natl. Acad. Sci. U.S.A. 113(33), 2016
PMID: 27482106
Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy.
Yilmazer-Hanke DM, Wolf HK, Schramm J, Elger CE, Wiestler OD, Blumcke I., J. Neuropathol. Exp. Neurol. 59(10), 2000
PMID: 11079781


Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®


PMID: 27959333
PubMed | Europe PMC

Suchen in

Google Scholar