Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders
Current Molecular Medicine May 4, 2015 Yuta Ohgi, Takashi Futamura, Kenji Hashimoto 109 citations
Glutamate, a major excitatory neurotransmitter, is crucial for synaptic plasticity including long-term potentiation and new synapse formation. Evidence links glutamate signaling to psychiatric disorders like schizophrenia, major depressive disorder, and bipolar disorder. Postmortem brain studies show altered spine density in these conditions, suggesting remodeled neuronal circuits contribute to their pathobiology. Drugs targeting the glutamate system, particularly the NMDA receptor antagonist ketamine, show rapid and robust antidepressant effects in treatment-resistant patients, unlike conventional antidepressants. Animal studies indicate ketamine induces rapid synaptogenesis, implicating NMDA receptor signaling in depression treatment. This review summarizes glutamate's role in dendritic spine formation and remodeling, discusses abnormalities from postmortem and animal studies, and reviews potential benefits of NMDA receptor-acting drugs.