Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders
Yuta Ohgi, Takashi Futamura, Kenji Hashimoto
Current Molecular Medicine May 4, 2015 DOI: 10.2174/1566524015666150330143008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Neuroplasticity |
| Keywords | Synaptogenesis Nmda receptor Glutamate receptor Schizophrenia object-oriented programming Antidepressant Mood disorders Dendritic spine Long-term potentiation Synapse Hippocampus Cognition Hippocampal formation |
| Citations | 109 |
| Key findings | Glutamate signaling, particularly through NMDA receptors, is implicated in psychiatric disorders and drugs like ketamine show rapid antidepressant effects via synaptogenesis. |
Abstract
Glutamate, a major excitatory neurotransmitter, plays important roles in synaptic plasticity, such as long-term potentiation (LTP) and new synapse formation. Growing evidence suggests that glutamate signaling is involved in the neurobiology of psychiatric disorders, including schizophrenia, major depressive disorder (MDD) and bipolar disorder (BP). Postmortem brain studies demonstrated altered spine density in brains from patients with these psychiatric disorders, indicating that remodeled neuronal circuits may contribute to the pathobiology of these psychiatric diseases. Drugs targeting the glutamate system have typically attracted attention as they show efficacy in animal studies and potential therapeutic effects in the clinical setting. In particular, the Nmethyl- D-aspartate (NMDA) receptor antagonist, ketamine exerts a rapid and robust antidepressant effect in treatment-resistant patients with MDD and BP, whereas conventional antidepressants require several weeks for therapeutic onset. Animal studies showed that ketamine induced rapid synaptogenesis, suggestive of synaptic plasticity via NMDA receptor signaling being an essential event in the treatment of depression. Therefore, drugs modulating glutamate signaling could also be potential therapeutic drugs for psychiatric disorders. First, we summarize the role of glutamate signaling on dendritic spine formation, maintenance and remodeling. Then, we discuss the abnormalities identified in dendritic spine and glutamate signaling from postmortem brain studies and animal models of psychiatric disorders. Finally, we review the potential benefits of drugs acting on the NMDA receptor in clinical and animal models of psychiatric disorders.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 17
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model. Biological Psychiatry 2018
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
- Rapid and Sustained Antidepressant Action of the mGlu2/3 Receptor Antagonist MGS0039 in the Social Defeat Stress Model: Comparison with Ketamine The International Journal of Neuropsychopharmacology October 7, 2016
and 12 more in the library