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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Prediction of Mutations in H3N2 Hemagglutinins of Influenza A Virus from North America Based on Different Datasets
Protein & Peptide Letters Anti-Tubercular and Anti-Inflammatory Activities of Azetidin-2-One Derivatives and Their Effects on the Activity of Phospholipase A2
Medicinal Chemistry High Frequency of the Opioid Receptor µ-1 (OPRM1) A118G Polymorphism, an Opioid Drug Therapy Related Gene, in the Indonesian Population
Current Pharmacogenomics and Personalized Medicine Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components for Cancer Management
Current Medicinal Chemistry Recent Advances in Physical Approaches for Transdermal Penetration Enhancement
Current Drug Therapy What Can Neuroscience Tell Us About the Potential of Psychedelics in Healthcare? How the Neurophenomenology of Psychedelics Research Could Help us to Flourish Throughout Our Lives, as Well as to Enhance Our Dying
Current Drug Abuse Reviews Design and Synthesis Three Steroid-Tetraone Derivatives Using Testosterone as Chemical Tool
Letters in Organic Chemistry Patent Review of Novel Nanostructrued Devices, Nanofabrication Methods and Applications in Nanofluidics and Nanomedicine
Recent Patents on Nanotechnology The Potency of Refined Mouse Models: Implications for Clinical Trials
Current Cancer Therapy Reviews Determination of three Unsaturated Fatty Acids in Pressure Ulcer Rats Using A UPLC-MS/MS Method
Current Pharmaceutical Analysis Archaeosome Immunostimulatory Vaccine Delivery System
Current Drug Delivery Relaxed Statistical Shape Models for 3D Image Segmentation – Application to Mandible Bone in Cone-beam CT Data
Current Medical Imaging Tumour Targeting with Systemically Administered Bacteria
Current Gene Therapy Subcellular Analysis of the Platelet Proteome
Current Proteomics Effects of Nanoscale Confinement on the Functionality of Nucleic Acids: Implications for Nanomedicine
Current Medicinal Chemistry Techniques of Structural Characterization of Dendrimers
Current Organic Chemistry A Three-gene-based Type 1 Diabetes Diagnostic Signature
Current Pharmaceutical Design Nanosuspension: A Potential Nanoformulation for Improved Delivery of Poorly Bioavailable Drug
Micro and Nanosystems Aldo-Keto Reductase Family 1 Member B1 Inhibitors: Old Drugs with New Perspectives
Recent Patents on Anti-Cancer Drug Discovery A Synopsis on the Role of Human Papilloma Virus Infection in Cervical Cancer
Current Drug Metabolism