PMID- 38195548
OWN - NLM
STAT- MEDLINE
DCOM- 20240111
LR  - 20240116
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan 9
TI  - D-Cycloserine enhances the bidirectional range of NMDAR-dependent hippocampal 
      synaptic plasticity.
PG  - 18
LID - 10.1038/s41398-023-02725-7 [doi]
LID - 18
AB  - The partial N-methyl-D-aspartate receptor (NMDAR) agonist D-Cycloserine (DCS) has 
      been evaluated for the treatment of a wide variety of psychiatric disorders, 
      including dementia, schizophrenia, depression and for the augmentation of 
      exposure-based psychotherapy. Most if not all of the potential psychiatric 
      applications of DCS target an enhancement or restitution of cognitive functions, 
      learning and memory. Their molecular correlate is long-term synaptic plasticity; 
      and many forms of synaptic plasticity depend on the activation of NMDA receptors. 
      Here, we comprehensively examined the modulation of different forms of synaptic 
      plasticity in the hippocampus by DCS and its mechanism. We found that DCS 
      positively modulates NMDAR-dependent forms of long-term synaptic plasticity 
      (long-term synaptic potentiation, LTP, and long-term synaptic depression, LTD) in 
      hippocampal brain slices of juvenile rats without affecting basal synaptic 
      transmission. DCS binds to the D-serine/glycine binding site of the NMDAR. 
      Pharmacological inhibition of this site prevented the induction of LTP, whereas 
      agonism at the D-serine/glycine binding site augmented LTP and could functionally 
      substitute for weak LTP induction paradigms. The most probable origin of 
      endogenous D-serine are astrocytes, and its exocytosis is regulated by astrocytic 
      metabotropic glutamate receptors (mGluR1). Functional eradication of astrocytes, 
      inhibition of mGluR1 receptors and G-protein signaling in astrocytes adjacent to 
      postsynaptic neurons prevented the induction of NMDAR-dependent forms of LTP and 
      LTD. Our results support the enhancement of a bidirectional range of 
      NMDAR-dependent hippocampal synaptic plasticity by DCS and D-serine-mediated 
      gliotransmission. Therefore, the D-serine/glycine-binding site in NMDAR is a 
      major target for psychopharmacological interventions targeting plasticity-related 
      disorders.
CI  - (c) 2024. The Author(s).
FAU - Vestring, Stefan
AU  - Vestring S
AUID- ORCID: 0000-0001-9150-8712
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany. stefan.vestring@uniklinik-freiburg.de.
AD  - Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, 
      University of Freiburg, D-79110, Freiburg, Germany. 
      stefan.vestring@uniklinik-freiburg.de.
FAU - Dorner, Alexandra
AU  - Dorner A
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Scholliers, Jonas
AU  - Scholliers J
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Ehrenberger, Konstantin
AU  - Ehrenberger K
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Kiss, Andrea
AU  - Kiss A
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Arenz, Luis
AU  - Arenz L
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Theiss, Alice
AU  - Theiss A
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Rossner, Paul
AU  - Rossner P
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Frase, Sibylle
AU  - Frase S
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Du Vinage, Catherine
AU  - Du Vinage C
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Wendler, Elisabeth
AU  - Wendler E
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
FAU - Serchov, Tsvetan
AU  - Serchov T
AUID- ORCID: 0000-0002-2234-2875
AD  - Centre National de la Recherche Scientifique (CNRS) UPR3212, Universite de 
      Strasbourg, Institut des Neurosciences Cellulaires et Integratives (INCI), 
      Strasbourg, France.
AD  - University of Strasbourg, Institute for Advanced Study (USIAS), Strasbourg, 
      France.
FAU - Domschke, Katharina
AU  - Domschke K
AUID- ORCID: 0000-0002-2550-9132
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
AD  - Center for Basics in Neuromodulation (NeuoModulBasics), Faculty of Medicine, 
      University of Freiburg, D-79106, Freiburg, Germany.
FAU - Bischofberger, Josef
AU  - Bischofberger J
AD  - Department of Biomedicine, University of Basel, CH-4056, Basel, Switzerland.
FAU - Normann, Claus
AU  - Normann C
AUID- ORCID: 0000-0001-5693-8936
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, 
      Germany.
AD  - Center for Basics in Neuromodulation (NeuoModulBasics), Faculty of Medicine, 
      University of Freiburg, D-79106, Freiburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20240109
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 95IK5KI84Z (Cycloserine)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 452VLY9402 (Serine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Rats
MH  - *Cycloserine/pharmacology
MH  - *Receptors, N-Methyl-D-Aspartate
MH  - Neuronal Plasticity
MH  - Serine
MH  - Glycine
MH  - Hippocampus
PMC - PMC10776623
COIS- The authors declare no competing interests.
EDAT- 2024/01/10 00:42
MHDA- 2024/01/11 07:42
PMCR- 2024/01/09
CRDT- 2024/01/09 23:40
PHST- 2022/09/26 00:00 [received]
PHST- 2023/12/21 00:00 [accepted]
PHST- 2023/11/24 00:00 [revised]
PHST- 2024/01/11 07:42 [medline]
PHST- 2024/01/10 00:42 [pubmed]
PHST- 2024/01/09 23:40 [entrez]
PHST- 2024/01/09 00:00 [pmc-release]
AID - 10.1038/s41398-023-02725-7 [pii]
AID - 2725 [pii]
AID - 10.1038/s41398-023-02725-7 [doi]
PST - epublish
SO  - Transl Psychiatry. 2024 Jan 9;14(1):18. doi: 10.1038/s41398-023-02725-7.