Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats

DeMar, James C.; Lee, Ho‐Joo; Ma, Kaizong; Chang, Lisa; Bell, Jane M.; Rapoport, Stanley I.; Bazinet, Richard P.

doi:10.1016/j.bbalip.2006.06.006

Cited by 141 publications

(139 citation statements)

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“…Although this study focused on n-3 PUFA kinetics and concentrations, future studies should test the effects of aging on n-6 PUFA liver kinetics. Rates of incorporation of unesterified circulating DHA and AA into brain reflect their respective rates of loss from brain due to metabolism, as the shorter chain PUFAs that enter brain largely undergo rapid oxidation (Demar et al 2005;DeMar et al 2006;Chen et al 2009;Chen et al 2011). As biomarkers of brain PUFA integrity, unesterified plasma DHA and AA concentrations may be more informative than the respective esterified concentrations (Kuriki et al 2003;Rapoport et al 2011).…”

Section: Ementioning

confidence: 99%

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Gao

Taha

et al. 2012

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Docosahexaenoic acid (DHA,, an n-3 polyunsaturated fatty acid (PUFA) found at high concentrations in brain and retina and critical to their function, can be obtained from fish products or be synthesized from circulating α-linolenic acid (α-LNA, 18:3n-3) mainly in the liver. With aging, liver synthetic enzymes are reported reduced or unchanged in the rat. To test whether liver synthesis-secretion of DHA from α-LNA changes with age, we measured whole-body DHA conversion coefficients and rates in unanesthetized adult male Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA, 20:5n-3)-and DHAcontaining diet. Unesterified [U-13 C]α-LNA bound to albumin was infused intravenously for 2 h, while [ 13 C]-esterified n-3 PUFAs were measured in arterial plasma, as were unlabeled unesterified and esterified PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with age, but esterified n-3 PUFA concentrations did not change significantly. Calculated conversion coefficients were not changed significantly with age, whereas synthesis-secretion rates (product of conversion coefficient and unesterified plasma α-LNA concentration) of esterified DHA and n-3 DPA were reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas half-lives increased. The results suggest that hepatic capacity to synthesize DHA and other n-3 PUFAs from circulating α-LNA is maintained with age in the rat, but that reduced plasma α-LNA availability reduces net synthesis-secretion. As unesterified plasma DHA is the form that is incorporated preferentially into brain phospholipid, its reduced synthesis may be deleterious to brain function in aged rats.

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Section: Ementioning

confidence: 99%

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Gao

Taha

et al. 2012

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“…Although it can be synthesized from the nutritionally essential polyunsaturated fatty acid linoleic acid (18:2nÀ6), the rate of this reaction appears to be slow, 29 especially within the brain. 30 Thus, brain AA likely originates from the diet and/or from conversion of dietary linoleic acid in the liver. [31][32][33][34] Earlier studies implicated AA as essential for growth and development, 35 but it is now recognized that AA is also extensively involved in brain signaling 36,37 via serotonergic, 38,39 glutamatergic, 40,41 dopaminergic 42,43 and cholinergic 44,45 receptor stimulation.…”

Section: Overview Of the Aa Cascadementioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

107

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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“…The quantity lost is replaced rapidly by diet-derived nonesterified AA in plasma, since AA cannot be synthesized de novo in mammalian tissue and its precursor, linoleic acid (18:2 n-6), is not significantly elongated to AA in the adult brain (DeMar et al, 2004;Holman, 1986). Replacement is proportional to PLA 2 activation and can be imaged by injecting radiolabeled AA intravenously and measuring regional brain AA incorporation coefficients k* (brain radioactivity/integrated plasma radioactivity) using quantitative autoradiography.…”

Section: Introductionmentioning

confidence: 99%

Chronic Lithium Chloride Administration to Unanesthetized Rats Attenuates Brain Dopamine D2-Like Receptor-Initiated Signaling Via Arachidonic Acid

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

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We studied the effect of lithium chloride on dopaminergic neurotransmission via D 2 -like receptors coupled to phospholipase A 2 (PLA 2 ). In unanesthetized rats injected i.v. with radiolabeled arachidonic acid (AA, 20:4 n-6), regional PLA 2 activation was imaged by measuring regional incorporation coefficients k* of AA (brain radioactivity divided by integrated plasma radioactivity) using quantitative autoradiography, following administration of the D 2 -like receptor agonist, quinpirole. In rats fed a control diet, quinpirole at 1 mg/kg i.v. increased k* for AA significantly in 17 regions with high densities of D 2 -like receptors, of 61 regions examined. Increases in k* were found in the prefrontal cortex, frontal cortex, accumbens nucleus, caudate-putamen, substantia nigra, and ventral tegmental area. Quinpirole, 0.25 mg/kg i.v. enhanced k* significantly only in the caudate-putamen. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, neither 0.25 mg/kg nor 1 mg/kg quinpirole increased k* significantly in any region. Orofacial movements following quinpirole were modified but not abolished by LiCl feeding. The results suggest that downregulation by lithium of D 2 -like receptor signaling involving PLA 2 and AA may contribute to lithium's therapeutic efficacy in bipolar disorder.

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Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats

Cited by 141 publications

References 55 publications

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Chronic Lithium Chloride Administration to Unanesthetized Rats Attenuates Brain Dopamine D2-Like Receptor-Initiated Signaling Via Arachidonic Acid

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