title: Acute Footshock Stress Induces Time-Dependent Modifications of AMPA/NMDA Protein Expression and AMPA Phosphorylation.
abstract: Clinical studies on patients with stress-related neuropsychiatric disorders reported functional and morphological changes in brain areas where glutamatergic transmission is predominant, including frontal and prefrontal areas. In line with this evidence, several preclinical works suggest that glutamate receptors are targets of both rapid and long-lasting effects of stress. Here we found that acute footshock- (FS-) stress, although inducing no transcriptional and RNA editing alterations of ionotropic AMPA and NMDA glutamate receptor subunits, rapidly and transiently modulates their protein expression, phosphorylation, and localization at postsynaptic spines in prefrontal and frontal cortex. In total extract, FS-stress increased the phosphorylation levels of GluA1 AMPA subunit at Ser(845) immediately after stress and of GluA2 Ser(880) 2 h after start of stress. At postsynaptic spines, stress induced a rapid decrease of GluA2 expression, together with an increase of its phosphorylation at Ser(880), suggesting internalization of GluA2 AMPA containing receptors. GluN1 and GluN2A NMDA receptor subunits were found markedly upregulated in postsynaptic spines, 2 h after start of stress. These results suggest selected time-dependent changes in glutamatergic receptor subunits induced by acute stress, which may suggest early and transient enhancement of AMPA-mediated currents, followed by a transient activation of NMDA receptors.
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonini
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mora
authors.affiliation: Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tornese
authors.affiliation: Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sala
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Filippini
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: La Via
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology and Center of Excellence for Biomedical Research, University of Genoa, 16148 Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Milanese
authors.affiliation: Unit of Biostatistics and Biomathematics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology and Center of Excellence for Biomedical Research, University of Genoa, 16148 Genoa, Italy.
authors.forename: Gianbattista
authors.initials: G
authors.lastname: Bonanno
authors.affiliation: Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy; Genetic Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
authors.affiliation: Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.affiliation: Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.affiliation: Biology and Genetic Division, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004597:Electroshock; D008297:Male; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D003345:Corticosterone