title: A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system.
abstract: 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.
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Floranópolis, Brazil.
authors.forename: M W
authors.initials: MW
authors.lastname: Lopes
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Floranópolis, Brazil.|Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: Leal
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Epilepsy Center of Santa Catarina, Federal University of Santa Catarina, Florianópolis, Brazil.|Neurosurgery Unit, Governador Celso Ramos Hospital, Florianópolis, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Guarnieri
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: M L
authors.initials: ML
authors.lastname: Schwarzbold
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Floranópolis, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Hoeller
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Diaz
authors.affiliation: Anesthesiology Division, Hospital Governador Celso Ramos, Florianópolis, Brazil.
authors.forename: G L
authors.initials: GL
authors.lastname: Boos
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Epilepsy Center of Santa Catarina, Federal University of Santa Catarina, Florianópolis, Brazil.|Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Neurosurgery Unit, Governador Celso Ramos Hospital, Florianópolis, Brazil.|Department of Surgery, HU, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: M N
authors.initials: MN
authors.lastname: Linhares
authors.affiliation: Pathology Division, HU, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: J C
authors.initials: JC
authors.lastname: Nunes
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.|Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.|Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Brazil.|Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Bortolotto
authors.affiliation: Physiological Psychology, University of Bielefeld, Bielefeld, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Markowitsch
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.|Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.affiliation: Center for Applied Neuroscience, Hospital Universitário, Federal University of Santa Catarina, Florianópolis, Brazil.|Epilepsy Center of Santa Catarina, Federal University of Santa Catarina, Florianópolis, Brazil.|Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Walz
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004833:Epilepsy, Temporal Lobe / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000601:surgery; D006801:Humans; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013702:Temporal Lobe / Q000187:drug effects / Q000601:surgery
chemical_list: D000893:Anti-Inflammatory Agents; D018091:Receptors, AMPA; D003907:Dexamethasone