Prostaglandins, leukotrienes, and essential fatty acids最新文献

{"title":"Apolipoprotein D modulates arachidonic acid signaling in cultured cells: implications for psychiatric disorders.","authors":"Elizabeth A Thomas,&nbsp;Roshni C George,&nbsp;J Gregor Sutcliffe","doi":"10.1016/j.plefa.2003.08.014","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.014","url":null,"abstract":"<p><p>Deficiencies in arachidonic acid (AA) parameters have been reported in schizophrenic patients. AA is a primary binding ligand for apolipoprotein D (apoD), which is increased in response to antipsychotic drug treatment and elevated in subjects with schizophrenia and bipolar disorder. In this study, we investigated whether apoD might modulate AA signaling/mobilization in cultured embryonic kidney (HEK) 293T cells. Immunofluorescent labeling revealed both cytosolic and membrane-bound expression of apoD protein in apoD-transfected cells. In cells expressing apoD, phorbal 12-myristate 13-acetate-induced AA release was inhibited compared to controls and membrane levels of AA were elevated, as indicated by the amount of AA maximally incorporated into membrane phospholipids. In addition, exogenous apoD added directly to the incubation media prevented cellular uptake of free [3H]AA. These results suggest that apoD acts to stabilize membrane-associated AA by preventing release and sequestering free AA in the cell. These actions of apoD may be beneficial to psychiatric patients.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents.","authors":"J Xu,&nbsp;M Chalimoniuk,&nbsp;Y Shu,&nbsp;A Simonyi,&nbsp;A Y Sun,&nbsp;F A Gonzalez,&nbsp;G A Weisman,&nbsp;W G Wood,&nbsp;G Y Sun","doi":"10.1016/j.plefa.2003.08.016","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.016","url":null,"abstract":"<p><p>Upregulation and activation of phospholipases A2 (PLA2) and cyclooxygenases (COX) leading to prostaglandin E2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1beta, TNFalpha and IFNgamma), the P2 nucleotide receptor agonist ATP, and oxidants (H2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia?","authors":"P D Skosnik,&nbsp;J K Yao","doi":"10.1016/j.plefa.2003.08.008","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.008","url":null,"abstract":"<p><p>Schizophrenia (SZ) is a devastating neuropsychiatric disorder affecting 1% of the general population, and is characterized by symptoms such as delusions, hallucinations, and blunted affect. While many ideas regarding SZ pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity. However, treatments based on this paradigm have met with only modest success, and current medications fail to alleviate symptoms in 30-60% of patients. An alternative idea postulated a quarter of a century ago by Feldberg (Psychol. Med. 6 (1976) 359) and Horrobin (Lancet 1 (1977) 936) involves the theory that SZ is associated in part with phospholipid/fatty acid abnormalities. Since then, it has been repeatedly shown that in both central and peripheral tissue, SZ patients demonstrate increased phospholipid breakdown and decreased levels of various polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA). Given the diverse physiological function of membrane phospholipids and PUFAs, an elucidation of their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. The purpose of this review is to summarize the relevant data on membrane phospholipid/PUFA defects in SZ, the physiological consequence of altered AA signaling, and how they relate to the neurobiological manifestations of SZ and therapeutic outcome.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults.","authors":"A J Richardson,&nbsp;E Cyhlarova,&nbsp;M A Ross","doi":"10.1016/j.plefa.2003.08.018","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.018","url":null,"abstract":"<p><p>Reduced omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes are often found in patients with schizophrenia. Here we investigated whether membrane concentrations of these fatty acids might vary as a function of schizotypal traits in non-psychotic individuals. Twenty-five healthy adults completed the O-LIFE schizotypal trait inventory and fatty acid composition of their venous blood samples was analysed via gas-liquid chromatography. Correlations between schizotypy measures and RBC fatty acids were examined and comparisons made between groups high and low on fatty acid measures and schizotypy scores. The omega-6 fatty acids arachidonic, adrenic and docosapentaenoic acid were directly related to positive schizotypal trait measures, as were most omega-3 fatty acids, but none were related to a negative, withdrawn form of schizotypy. Our findings of high RBC concentrations of omega-3 and omega-6 fatty acids in healthy adults with positive schizotypal traits clearly contrast with the low levels often found in schizophrenia, but are quite consistent with evidence that omega-3 fatty acids (notably EPA) can be useful in the treatment of schizophrenic illness.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24080500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane polyunsaturated fatty acids and CSF cytokines in patients with schizophrenia.","authors":"J K Yao,&nbsp;C G Sistilli,&nbsp;D P van Kammen","doi":"10.1016/j.plefa.2003.08.015","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.015","url":null,"abstract":"<p><p>Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia, suggesting defects in phospholipid metabolism and cell signaling in schizophrenia. The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids (PUFAs) were associated with an increased secretion of proinflammatory cytokines. Thus, we measured interleukin 6 (IL-6) and interleukin 10 (IL-10) in cerebrospinal fluid (CSF) of patients with chronic schizophrenia as well as PUFAs of red blood cell (RBC) membranes from the same individuals. A significant and inverse correlation was found between CSF IL-6 (not IL-10) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia. Specifically, such an association was found in the n-6 (18:2, 20:4, and 22:4) and, to a lesser extent, the n-3 fatty acids. Taken together, the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia, possibly resulting from an increased phospholipase A2 activity mediated through the proinflammatory cytokines.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between membrane pathology and language disorder in schizophrenia.","authors":"Ruth Condray,&nbsp;Angela G Glasgow","doi":"10.1016/j.plefa.2003.08.017","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.017","url":null,"abstract":"<p><p>Receptive language disorder in schizophrenia has been hypothesized to involve a fundamental deficit in the temporal (time-based) dynamics of brain function that includes disruptions to patterns of activation and synchronization. In this paper, candidate mechanisms and pathways that could account for this basic deficit are discussed. Parallels are identified between the patterns of language dysfunction observed for schizophrenia and dyslexia, two separate clinical disorders that may share a common abnormality in cell membrane phospholipids. A heuristic is proposed which details a trajectory involving an interaction of brain fatty acids and second-messenger function that modulates synaptic efficacy, and, in turn, influences language processing in schizophrenia patients. It is additionally hypothesized that a primary deficit of functional excitation originating in the cerebellum, in combination with a compensatory decrease of functional inhibition in the prefrontal cortex, influences receptive language dysfunction in schizophrenia.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia.","authors":"Ravinder Reddy,&nbsp;Matcheri S Keshavan","doi":"10.1016/j.plefa.2003.08.011","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.011","url":null,"abstract":"<p><p>A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the \"Membrane Hypothesis of Schizophrenia.\" The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (31P MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. 31P MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying 31P MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results.","authors":"Malcolm Peet","doi":"10.1016/j.plefa.2003.08.020","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.020","url":null,"abstract":"<p><p>It has been hypothesised that polyunsaturated fatty acids (PUFA) play an important role in the aetiology of schizophrenia and depression. Evidence supporting this hypothesis for schizophrenia includes abnormal brain phospholipid turnover shown by 31P Magnetic Resonance Spectroscopy, increased levels of phospholipase A2, reduced niacin skin flush response, abnormal electroretinogram, and reduced cell membrane levels of n-3 and n-6 PUFA. In depression, there is strong epidemiological evidence that fish consumption reduces risk of becoming depressed and evidence that cell membrane levels of n-3 PUFA are reduced. Four out of five placebo-controlled double- blind trials of eicosapentaenoic acid (EPA) in the treatment of schizophrenia have given positive findings. In depression, two placebo-controlled trials have shown a strong therapeutic effect of ethyl-EPA added to existing medication. The mode of action of EPA is currently not known, but recent evidence suggests that arachidonic acid (AA) if of particular importance in schizophrenia and that clinical improvement in schizophrenic patients using EPA treatment correlates with changes in AA.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24080501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment.","authors":"D R Evans,&nbsp;V V Parikh,&nbsp;M M Khan,&nbsp;C Coussons,&nbsp;P F Buckley,&nbsp;S P Mahadik","doi":"10.1016/j.plefa.2003.08.010","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.010","url":null,"abstract":"<p><p>A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at baseline, reduced levels of antioxidant enzymes were associated with increased plasma lipid peroxides and reduced membrane EPUFAs, particularly omega-3 fatty acids. Furthermore, these biochemical measures normalized after 6 months of antipsychotic treatment. Parallel-improved psychopathology indicated that membrane EPUFA status might be partly affected by oxidative damage, which together may contribute to the pathophysiology and thereby, psychopathology of schizophrenia. These data also support the augmentation of antipsychotic treatment by supplementation with a combination of antioxidants and omega-3 fatty acids.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phospholipid and eicosanoid signaling disturbances in schizophrenia.","authors":"Brian M Ross","doi":"10.1016/j.plefa.2003.08.012","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.08.012","url":null,"abstract":"<p><p>A variety of biochemical, clinical and genetic evidence suggests that phospholipid metabolism may play an aetiological role in schizophrenia. A key piece of evidence is the reduced vasodilatory response of patients with schizophrenia to nicotinic acid (NA). NA causes vasodilation via the activation of phospholipase A2 (PLA2) leading to the release of free fatty acids from membrane phospholipids and the subsequent production of prostaglandins. Insensitivity to NA may be due to a 'block' in the downstream signaling pathway used by the drug to evoke its response. It can be argued that if such an abnormality occurs in neurons, impaired PLA2-dependent signaling could result in altered glutamateric and dopaminergic transmission in such a way as to produce or exacerbate psychotic symptoms. The complimentary finding of increased PLA2 activity in schizophrenia may be an attempt to overcome the signaling block. It is suggested that intervention aimed at increasing the activity of PLA2-dependent signaling systems may be therapeutically useful in the treatment of the illness.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.08.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24081104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}