Mechanism Of Lithium Action For The Treatment Of Bipolar Disorder

Main Category: Bipolar
Also Included In: Depression
Article Date: 15 May 2006 - 0:00 PDT

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Calcium is a common intracellular signaling molecule with a wide range of functions in the brain, and the regulation as well as dysregulation of calcium signaling via the principal intracellular calcium release channel, InsP3R1, has been linked to many normal cellular processes as well as neurological diseases. In addition, the calcium binding protein, neuronal calcium sensor-1 (NCS-1), has been shown to regulate calcium signaling and NCS-1 expression is increased in bipolar patients. In a study appearing online on May 11 in advance of print publication in the June issue of the Journal of Clinical Investigation, Barbara E. Erhlich and colleagues from Yale University set out to determine if NCS-1 and InsP3R1 interact with each and if this interaction was altered in neuropathological disorders. They found that, in intact rat cells, NCS-1 dramatically increased the rate at which the InsP3R channel opened and released calcium, which would result in enhanced calcium signals at synapses in the brain. As lithium was introduced over a half-century ago for the treatment of the alternating occurrence of mania and depression that is characteristic of bipolar disorder, the authors tested the effect of lithium on the interaction between NCS-1 and InsP3R1. Therapeutic levels of lithium were found to block the effect of NCS-1 on InsP3R1 function, suggesting that the InsP3R1/NCS-1 interaction is an essential part of the mechanism of bipolar disorder. The study reveals the role of NCS-1 and suggests that it is a promising target for the treatment of neuropsychiatric disorders.

TITLE: Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

https://www.the-jci.org/article.php?id=22466

Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
http://www.jci.org/

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