Bipolar disorder is a major medical, social and economic burden worldwide. However, the biochemical basis of the disorder and the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review how combining a kinetic approach to studying the turnover of fatty acids within brain phospholipids of unanesthetized rats along with chronic administration of antimanic drugs (lithium, valproate and carbamazepine) at therapeutically relevant doses, shows that the brain arachidonic acid cascade is a common target of these drugs. The overlapping effects of the three drugs are decreased turnover of arachidonic acid but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E(2). Whereas lithium and carbamazepine target the transcription of the arachidonic acid-selective calcium-dependent cytosolic phospholipase A(2), valproate is a non-competitive inhibitor of an arachidonic acid-selective acyl-CoA synthetase. Two potential models of bipolar disorder, chronic N-methyl-d-aspartate and n-3 polyunsaturated fatty acid deprivation, opposite to the antimanic drugs, increase the turnover and markers of the arachidonic acid cascade in rat brain. These observations support the hypothesis proposed by Rapoport and colleagues that the arachidonic acid cascade is a common target of mood stabilizers and that by targeting substrate-specific enzymes the turnover of individual fatty acids can be regulated within the brain.
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http://dx.doi.org/10.1016/j.plefa.2007.10.018 | DOI Listing |
Antioxid Redox Signal
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Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
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National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd, Dong-E Country, Shandong Province, China.
Weaning is essential for foal growth and development. We determined the intestinal flora structure of donkey foals at the end of weaning (PreW_4d) and three stages after weaning (PostW_4d, PostW_8d, and PostW_15d) to explore the effects of weaning on intestinal development of donkey foals. The results showed that the main microbial flora in the gut of the donkey foal were Firmicutes and Bacteroides, and the proportion of Firmicutes gradually increased with weaning, which was an important reflection of the donkey foal's adaptability to the transition from lactose liquid feed to plant fiber solid feed.
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Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
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Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (FADS1), delta-6 desaturase (FADS2), and elongase (ELOVL2) on changes in RBC and plasma biomarkers.
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2nd Abdominal Surgery Department, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China.
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