Vol 6 n° 2 - Neuroplasticity
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espite the devastating impact that mood disor- ders have on the lives of millions worldwide, there is still a dearth of knowledge concerning their underlying etiology and pathophysiology.The brain systems that have hereto- fore received the greatest attention in neurobiological studies of mood disorders have been the monoaminergic neurotransmitter systems, which are extensively distrib- uted throughout the network of limbic, striatal, and pre- frontal cortical neuronal circuits thought to support the behavioral and visceral manifestations of mood disor- ders.1-3 Thus, clinical studies over the past 40 years have attempted to uncover the specific defects in these neuro- transmitter systems in mood disorders by utilizing a vari- ety of biochemical and neuroendocrine strategies. 1 4 3 B a s i c   r e s e a r c h D Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking Jing Du, MD, PhD; Jorge A. Quiroz, MD; Neil A. Gray, BS; Steve T. Szabo, PhD; Carlos A. Zarate Jr, MD; Husseini K. Manji, MD, FRCPC There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reduc- tions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamatergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treat- ment of mood disorders. Glutamate -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit traf- ficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plas- ticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affect- ing synaptic GluR1 represent novel therapies for these devastating illnesses. © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:143-155. Keywords: lithium; valproate; antidepressant; bipolar disorder; glutamate receptor GluR1; phosphorylation Author   affiliations:   Laboratory   of   Molecular   Pathophysiology,   National Institute of Mental Health, Bethesda, Md, USA Address for correspondence: Husseini K. Manji, MD, Laboratory of Molecular Pathophysiology,  Mood  and  Anxiety  Disorders  Program,  National  Institute  of Mental  Health,  9000  Rockville  Pike,  Building  10,  Unit  3  West,  Room  3s250, Bethesda, MD 20892, USA (e-mail: manjih@intra.nimh.nih.gov)