Possible role of prostaglandin E1 in the affective disorders and in alcoholism.

Horrobin, David F.; Manku, M.S.

doi:10.1136/bmj.280.6228.1363

Cited by 84 publications

(7 citation statements)

References 31 publications

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“…5 On the other hand, the arachidonic acid (AA, 20:4 n-6) cascade, which plays a key role in brain signaling, [6][7][8] could represent a target of lithium and other mood-stabilizers. Indeed, previous reports suggest a role for PGE 1 , a metabolite of dihomogamma-linolenic acid, in affective disorders, 9,10 but the exact mechanism by which the AA cascade is targeted has not been thoroughly investigated. This cascade involves phospholipase A 2 (PLA 2 )-mediated release from phospholipids of the polyunsaturated fatty acid (PUFA), AA, and its conversion to bioactive eicosanoids.…”

Section: Introductionmentioning

confidence: 99%

Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

et al. 2002

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Section: Introductionmentioning

confidence: 99%

Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

et al. 2002

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“…Twenty years ago, Horrobin and Manku had already noted the possible causative role of prostaglandins and their parent fatty acids in depression (69). In 1995, Hibbeln and Salem (70) proposed a link between the marked increase in depression rates in the 20th century (71) and increased intake of PUFAs containing omega-6 in the form of plant oils.…”

Section: Psychological Stressmentioning

confidence: 99%

Essential Fatty Acids and the Brain

2003

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Objective: To review the role of essential fatty acids in brain membrane function and in the genesis of psychiatric disease. Method: Medline databases were searched for published articles with links among the following key words: essential fatty acids, omega-3 fatty acids, docosahexanoic acid, eicosapentanoic acid, arachidonic acid, neurotransmission, phospholipase A2, depression, schizophrenia, mental performance, attention-deficit hyperactivity disorder, and Alzheimer's disease. Biochemistry textbooks were consulted on the role of fatty acids in membrane function, neurotransmission, and eicosanoid formation. The 3-dimensional structures of fatty acids were obtained from the Web site of the Biochemistry Department, University of Arizona (2001). Results: The fatty acid composition of neuronal cell membrane phospholipids reflects their intake in the diet. The degree of a fatty acid's desaturation determines its 3-dimensional structure and, thus, membrane fluidity and function. The ratio between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), in particular, influences various aspects of serotoninergic and catecholaminergic neurotransmission, as shown by studies in animal models. Phospholipase A2 (PLA2) hydrolyzes fatty acids from membrane phospholipids: liberated omega-6 PUFAs are metabolized to prostaglandins with a higher inflammatory potential, compared with those generated from the omega-3 family. Thus the activity of PLA2 coupled with membrane fatty acid composition may play a central role in the development of neuronal dysfunction. Intervention trials in human subjects show that omega-3 fatty acids have possible positive effects in the treatment of various psychiatric disorders, but more data are needed to make conclusive directives in this regard. Conclusion: The ratio of membrane omega-3 to omega-6 PUFAs can be modulated by dietary intake. This ratio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function.

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“…Altered levels of prostaglandins have been detected in different body fluids in patients with major affective disorders (23)(24)(25)(26)(27)(28). Also pharmacological evidence (29)(30)(31) suggests that altered prostaglandin metabolism may lead to mood disorders.…”

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confidence: 99%

Episode-Specific Differential Gene Expression of Peripheral Blood Mononuclear Cells in Rapid Cycling Supports Novel Treatment Approaches

Begemann

Sargin

Rossner

et al. 2008

Mol Med

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Molecular mechanisms underlying bipolar affective disorders are unknown. Difficulties arise from genetic and phenotypic heterogeneity of patients and the lack of animal models. Thus, we focused on only one patient (n = 1) with an extreme form of rapid cycling. Ribonucleic acid (RNA) from peripheral blood mononuclear cells (PBMC) was analyzed in a three-tiered approach under widely standardized conditions. Firstly, RNA was extracted from PBMC of eight blood samples, obtained on two consecutive days within one particular episode, including two different consecutive depressive and two different consecutive manic episodes, and submitted to (1) screening by microarray hybridizations, followed by (2) detailed bioinformatic analysis, and (3) confirmation of episode-specific regulation of genes by quantitative real-time polymerase chain reaction (qRT-PCR). Secondly, results were validated in additional blood samples obtained one to two years later. Among gene transcripts elevated in depressed episodes were prostaglandin D synthetase (PTGDS) and prostaglandin D2 11-ketoreductase (AKR1C3), both involved in hibernation. We hypothesized them to account for some of the rapid cycling symptoms. A subsequent treatment approach over 5 months applying the cyclooxygenase inhibitor celecoxib (2 × 200 mg daily) resulted in reduced severity rating of both depressed and manic episodes. This case suggests that rapid cycling is a systemic disease, resembling hibernation, with prostaglandins playing a mediator role.

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Possible role of prostaglandin E1 in the affective disorders and in alcoholism.

Cited by 84 publications

References 31 publications

Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

Essential Fatty Acids and the Brain

Episode-Specific Differential Gene Expression of Peripheral Blood Mononuclear Cells in Rapid Cycling Supports Novel Treatment Approaches

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