52 research outputs found

    NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity

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    Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders

    On possible reasons of positive near-anode voltage drop in high-current vacuum arc

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    In this paper we consider some reasons for the occurrence of a positive near-anode potential drop during current constriction in high-current vacuum arc. It is shown that if the radius of constriction is much larger than the electron mean free path, then a positive voltage drop in the near-anode plasma sheath does not occur, but an additional drop may occur in the near-anode plasma layer due to the anomalous resistance. If the current constriction radius is much less than the electron mean free path, then a positive voltage drop in the sheath arises under the usual condition, and the kinetic instabilities in the near-anode plasma do not develop. © 2019 IOP Publishing Ltd. All rights reserved.Russian Foundation for Basic Research, RFBR: 17-02-00346, 18-08-00547Russian Academy of Sciences, RASNational Natural Science Foundation of China, NSFC: 5191153011318-2-2-16This work was supported in part by RFBR(grant Nos. 17-02-00346, 18-08-00547, 19-08-00783, 19-58-53006), by RAS Program (project No. 11) and UB RAS Program (project No. 18-2-2-16), as well as by National Natural Science Foundation of China (project No. 51911530113)

    Inhibition of the Progesterone Nuclear Receptor during the Bone Linear Growth Phase Increases Peak Bone Mass in Female Mice

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    Augmentation of the peak bone mass (PBM) may be one of the most effective interventions to reduce the risk of developing osteoporosis later in life; however treatments to augment PBM are currently limited. Our study evaluated whether a greater PBM could be achieved either in the progesterone nuclear receptor knockout mice (PRKO) or by using a nuclear progesterone receptor (nPR) antagonist, RU486 in mice. Compared to their wild type (WT) littermates the female PRKO mice developed significantly higher cancellous and cortical mass in the distal femurs, and this was associated with increased bone formation. The high bone mass phenotype was partially reproduced by administering RU486 in female WT mice from 1–3 months of age. Our results suggest that the inhibition of the nPR during the rapid bone growth period (1–3 months) increases osteogenesis, which results in acquisition of higher bone mass. Our findings suggest a crucial role for progesterone signaling in bone acquisition and inhibition of the nPR as a novel approach to augment bone mass, which may have the potential to reduce the burden of osteoporosis
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