Abstract
Bipolar disorder (BD) is a severe psychiatric illness characterized by recurrent manic and depressive episodes, without a characteristic neuropathology or clear etiology. Drugs effective in BD target many key signaling pathways in animal and cell studies. However, their mode of action in the BD brain remains elusive. In the rat brain, some of the mood stabilizers effective in treating mania (lithium, carbamazepine, valproate) or depression (lamotrigine) in BD are reported to decrease transcription of cytosolic phospholipase A2 and cyclooxygenase-2 and to reduce levels of AP-2 and NF-κB, transcription factors of the two enzymes. The anti-manic drugs also decrease arachidonic acid (AA) turnover in brain phospholipids when given chronically to rats. Thus, drugs effective in BD commonly target AA cascade kinetics as well as AA cascade enzymes and their transcription factors in the rat brain. These studies suggest that of BD is associated with increased AA signaling in the brain. Developing therapeutic agents that suppress brain AA signaling could lead to additional treatments for BD. In this review, we discuss the mechanisms of action of mood stabilizers and the effects of docosahexaenoic acid on AA cascade enzymes in relation to BD.
Keywords: Bipolar disorder, cPLA2, sPLA2, COX-2, AP-2, NF-κB, arachidonic acid, mood stabilizers
Current Molecular Pharmacology
Title: Mood-Stabilizers Target the Brain Arachidonic Acid Cascade
Volume: 2
Author(s): Jagadeesh S. Rao and Stanley I. Rapoport
Affiliation:
Keywords: Bipolar disorder, cPLA2, sPLA2, COX-2, AP-2, NF-κB, arachidonic acid, mood stabilizers
Abstract: Bipolar disorder (BD) is a severe psychiatric illness characterized by recurrent manic and depressive episodes, without a characteristic neuropathology or clear etiology. Drugs effective in BD target many key signaling pathways in animal and cell studies. However, their mode of action in the BD brain remains elusive. In the rat brain, some of the mood stabilizers effective in treating mania (lithium, carbamazepine, valproate) or depression (lamotrigine) in BD are reported to decrease transcription of cytosolic phospholipase A2 and cyclooxygenase-2 and to reduce levels of AP-2 and NF-κB, transcription factors of the two enzymes. The anti-manic drugs also decrease arachidonic acid (AA) turnover in brain phospholipids when given chronically to rats. Thus, drugs effective in BD commonly target AA cascade kinetics as well as AA cascade enzymes and their transcription factors in the rat brain. These studies suggest that of BD is associated with increased AA signaling in the brain. Developing therapeutic agents that suppress brain AA signaling could lead to additional treatments for BD. In this review, we discuss the mechanisms of action of mood stabilizers and the effects of docosahexaenoic acid on AA cascade enzymes in relation to BD.
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Cite this article as:
Rao S. Jagadeesh and Rapoport I. Stanley, Mood-Stabilizers Target the Brain Arachidonic Acid Cascade, Current Molecular Pharmacology 2009; 2 (2) . https://dx.doi.org/10.2174/1874467210902020207
DOI https://dx.doi.org/10.2174/1874467210902020207 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
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