Biomaterial Database

Mood-stabilizers target the brain arachidonic acid cascade. 2009

Jagadeesh S Rao, and Stanley I Rapoport

Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. jrao@mail.nih.gov

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 A(2) and cyclooxygenase-2 and to reduce levels of AP-2 and NF-kappaB, 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.

UI	MeSH Term	Description	Entries
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000928	Antidepressive Agents	Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.	Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D001714	Bipolar Disorder	A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.	Affective Psychosis, Bipolar,Bipolar Disorder Type 1,Bipolar Disorder Type 2,Bipolar Mood Disorder,Depression, Bipolar,Manic Depression,Manic Disorder,Manic-Depressive Psychosis,Psychosis, Manic-Depressive,Type 1 Bipolar Disorder,Type 2 Bipolar Disorder,Psychoses, Manic-Depressive,Bipolar Affective Psychosis,Bipolar Depression,Bipolar Disorders,Bipolar Mood Disorders,Depression, Manic,Depressions, Manic,Disorder, Bipolar,Disorder, Bipolar Mood,Disorder, Manic,Manic Depressive Psychosis,Manic Disorders,Mood Disorder, Bipolar,Psychoses, Bipolar Affective,Psychoses, Manic Depressive,Psychosis, Bipolar Affective,Psychosis, Manic Depressive
D016328	NF-kappa B	Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.	Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016718	Arachidonic Acid	An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.	(all-Z)-5,8,11,14-Eicosatetraenoic acid,Arachidonic Acid, (all-Z)-Isomer, 1-(14)C-Labeled,Arachidonic Acid, (all-Z)-isomer, 3H-Labeled,Arachidonic Acid, Ammonium Salt, (all-Z)-Isomer,Arachidonic Acid, Cerium Salt, (all-Z)-Isomer,Arachidonic Acid, Cesium Salt, (all-Z)-Isomer,Arachidonic Acid, Lithium Salt, (all-Z)-Isomer,Arachidonic Acid, Potassium Salt, (all-Z)-Isomer,Arachidonic Acid, Sodium Salt,Arachidonic Acid, Sodium Salt, (all-Z)-Isomer,Arachidonic Acid, Zinc Salt, (all-Z)-Isomer,Sodium Arachidonate,Vitamin F,Arachidonate, Sodium
D050656	Transcription Factor AP-2	A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.	AP-2 Enhancer Binding Protein,AP-2 alpha Protein,AP-2 beta Protein,AP-2 epsilon Protein,AP-2 gamma Protein,AP-2delta Protein,Activator Protein AP-2,Enhancer-Binding Protein AP-2,TFAP2B Protein,TFAP2alpha Protein,Transcription Factor AP-2 alpha Protein,Transcription Factor AP-2 beta Protein,Transcription Factor AP-2 delta Protein,Transcription Factor AP-2 epsilon Protein,Transcription Factor AP-2 gamma Protein,Transcription Factor AP-2alpha,Transcription Factor AP-2beta,Transcription Factor AP-2epsilon,Transcription Factor AP-2gamma,Transcription Factor AP2,Transcription Factor Ap-2delta,AP 2 Enhancer Binding Protein,AP 2 alpha Protein,AP 2 beta Protein,AP 2 gamma Protein,AP 2delta Protein,AP-2, Activator Protein,AP-2, Enhancer-Binding Protein,AP-2, Transcription Factor,AP-2alpha, Transcription Factor,AP-2beta, Transcription Factor,AP-2epsilon, Transcription Factor,AP-2gamma, Transcription Factor,Activator Protein AP 2,Ap-2delta, Transcription Factor,Enhancer Binding Protein AP 2,Transcription Factor AP 2,Transcription Factor AP 2 alpha Protein,Transcription Factor AP 2 beta Protein,Transcription Factor AP 2 delta Protein,Transcription Factor AP 2 epsilon Protein,Transcription Factor AP 2 gamma Protein,Transcription Factor AP 2alpha,Transcription Factor AP 2beta,Transcription Factor AP 2epsilon,Transcription Factor AP 2gamma,Transcription Factor Ap 2delta
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D051546	Cyclooxygenase 2	An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.	COX-2 Prostaglandin Synthase,Cyclo-Oxygenase II,Cyclooxygenase-2,PGHS-2,PTGS2,Prostaglandin H Synthase-2,COX 2 Prostaglandin Synthase,Cyclo Oxygenase II,Prostaglandin H Synthase 2,Prostaglandin Synthase, COX-2,Synthase, COX-2 Prostaglandin
D054513	Group IV Phospholipases A2	A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.	Phospholipases A2, Group IV,Cytosolic Phospholipase A2 alpha,Cytosolic Phospholipase A2 beta,Cytosolic Phospholipase A2 delta,Cytosolic Phospholipase A2 epsilon,Cytosolic Phospholipase A2 gamma,Group IV Cytosolic Phospholipase A2,Group IVA Phospholipase A2,Group IVA Phospholipases A2,Group IVB Phospholipase A2,Group IVB Phospholipases A2,Group IVC Phospholipase A2,Group IVC Phospholipases A2,Group IVD Phospholipase A2,Group IVD Phospholipases A2,Group IVE Phospholipase A2,Group IVE Phospholipases A2,Group IVF Phospholipase A2,Group IVF Phospholipases A2,PLA(2)-IV,PLA2-IV,Phospholipase A(2)alpha,Phospholipase A2 Group IVA,Phospholipase A2 IV,Phospholipase A2, Group IVB,Phospholipase A2, Group IVC,Phospholipase A2, Group IVD,Phospholipase A2, Group IVE,Phospholipase A2, Group IVF,Phospholipase A2-alpha,Phospholipase A2-beta,Phospholipase A2-gamma,cPLA2-alpha,cPLA2-gamma,Phospholipase A2 alpha,Phospholipase A2 beta,Phospholipase A2 gamma,cPLA2 alpha,cPLA2 gamma