title: Activation of NMDA receptors thickens the postsynaptic density via proteolysis.
abstract: The postsynaptic density (PSD) is a protein complex that is critical for synaptic transmission. Ultrastructural changes in the PSD are therefore likely to modify synaptic functions. In this study, we investigated the ultrastructural changes in the PSD in the hippocampal CA1 stratum radiatum following neuronal excitation. Oxygen-glucose deprivation-induced PSD thickening in hippocampal slice cultures was blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist MK801. To gain more insight into the mechanisms underlying NMDA receptor-mediated PSD thickening, we assessed the area, length, and thickness of the PSD after NMDA treatment. The PSDs thickened with just 2 min of NMDA receptor stimulation, and this treatment was considered sublethal. When N-acetyl-leucyl-leucyl-norleucinal, an inhibitor of calpain, cathepsins, and the proteasome, was applied, NMDA-induced PSD thickening was abolished. Furthermore, the calcium-induced calcium release inhibitor, ryanodine, reduced NMDA receptor-mediated PSD thickening. These results suggest that NMDA receptor activation induces PSD thickening by proteolysis through intracellular calcium increase, including that induced by calcium.
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan; RSC-University of Hyogo Leading Program Center, RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan. Electronic address: fukunaga@sci.u-hyogo.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukunaga
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Nakajima
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Hatano
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan; RSC-University of Hyogo Leading Program Center, RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kashino
authors.affiliation: Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan; RSC-University of Hyogo Leading Program Center, RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan. Electronic address: atsuo@sci.u-hyogo.ac.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D057907:Post-Synaptic Density / Q000187:drug effects / Q000648:ultrastructure*; D059748:Proteolysis; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D005947:Glucose
keywords: Hippocampal slice culture; NMDA receptor; Postsynaptic density thickening; Proteolysis