Journal
NEUROSCIENTIST
Volume 15, Issue 5, Pages 525-539Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1073858409336093
Keywords
glutamate; tripartite; bipolar disorder; ketamine; riluzole
Categories
Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002828, ZIAMH002857] Funding Source: NIH RePORTER
- Intramural NIH HHS [Z01 MH002828-05, Z01 MH002857-03] Funding Source: Medline
Ask authors/readers for more resources
Bipolar disorder and major depressive disorder are common, chronic, and recurrent mood disorders that affect the lives of millions of individuals worldwide. Growing evidence suggests that glutamatergic system dysfunction is directly involved in mood disorders. This article describes the role of the tripartite glutamatergic synapse, comprising presynaptic and post-synaptic neurons and glial cells, in the pathophysiology and therapeutics of mood disorders. Glutamatergic neurons and glia directly control synaptic and extrasynaptic glutamate levels/release through integrative effects that target glutamate excitatory amino acid transporters, postsynaptic density proteins, ionotropic receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA], N-methyl-D-aspartate [NAIDA], and kainate) and metabotropic receptors. This article also explores the glutamatergic modulators riluzole and ketamine, which are considered valuable proof-of-concept agents for developing the next generation of antidepressants and mood stabilizers. In therapeutically relevant paradigms ketamine preferentially targets postsynaptic AMPA/NMDA receptors, and riluzole preferentially targets presynaptic voltage-operated channels and glia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available