ArticleMolecular medicine (Cambridge, Mass.)2021
D-Serine produces antidepressant-like effects in mice through suppression of BDNF signaling pathway and regulation of synaptic adaptations in the nucleus accumbens.
Article in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Non-classical NMDAR subunit GluN3A in a specialized hippocampal region regulates stress-coping strategies in male mice.Communications biology · 2026Article
- Molecular Characterization of the Progressive Landscape of Depression.bioRxiv : the preprint server for biology · 2026Article
- Cell Type-Specific Downregulation of Dnmt3a in Nucleus Accumbens Oligodendrocytes Prevents Myelin Damage and Reduces Susceptibility to Social Stress in Male Mice.Biomolecules · 2026Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Temporomandibular disorders and mental health: shared etiologies and treatment approaches.The journal of headache and pain · 2025Review
- Administration of chiglitazar reverses chronic stress-induced depressive-like symptoms in mice via activation of hippocampal PPARα and BDNF.Frontiers in pharmacology · 2025Article
- NMDA Receptor Glycine Binding Site Modulators for Prevention and Treatment of Ketamine Use Disorder.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Promising Application of D-Amino Acids toward Clinical Therapy.International journal of molecular sciences · 2022Review
- Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- An Overview of the Involvement of D-Serine in Cognitive Impairment in Normal Aging and Dementia.Frontiers in psychiatry · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveD-Serine is a crucial endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs) in the central nervous system and can affect the function of the brain derived neurotrophic factor (BDNF) system, which plays an essential role in modulating synaptic plasticity. The current study aimed to systematically evaluate the role and mechanisms of D-serine in depressive behavior in nucleus accumbens (NAc).
methodsD-Serine concentration in the chronic social defeat stress (CSDS) model in NAc was measured using high-performance liquid chromatography (HPLC). The antidepressant-like effects of D-serine were identified using forced swim test (FST) and tail suspension test (TST) in control mice and then assessed in CSDS model. We applied social interaction and sucrose preference tests to identify the susceptibility of CSDS model. Western blotting was further performed to assess the changes of BDNF signaling cascade in NAc after CSDS and D-serine treatment. The BDNF signaling inhibitor (K252a) was also used to clarify the antidepressant-like mechanism of D-serine. Moreover, D-serine effects on synaptic plasticity in NAc were investigated using electrophysiological methods.
resultsD-Serine concentration was decreased in depression susceptible mice in NAc. D-Serine injections into NAc exhibited antidepressant-like effects in FST and TST without affecting the locomotor activity of mice. D-Serine was also effective in CSDS model of depression. Moreover, D-serine down-regulated the BDNF signaling pathway in NAc during CSDS procedure. Furthermore, BDNF signaling inhibitor (K252a) enhanced the antidepressant effects of D-serine. We also found that D-serine was essential for NMDARs-dependent long-term depression (LTD).
conclusionD-Serine exerts antidepressant-like effects in mice mediated through restraining the BDNF signaling pathway and regulating synaptic plasticity in NAc.
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