Title:Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders
Volume: 15
Issue: 3
Author(s): Y. Ohgi, T. Futamura and K. Hashimoto
Affiliation:
Keywords:
Animal model, glutamate, mood disorder, NMDA receptor, postmortem study, schizophrenia, spine
density.
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.
