Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation

Basselin, Mireille; Kim, Hyung‐Wook; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Murphy, Robert C.; Farias, Santiago

doi:10.1194/jlr.m002469

Cited by 49 publications

(60 citation statements)

References 64 publications

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“…Consistently, chronic lithium treatment significantly decreased lipopolysaccharide (LPS)-induced elevation in brain PGE 2 synthesis in rats. 28 This study 28 also showed that lithium significantly increased 17-hydroxy-docosahexanoic acid (17-hydroxy-DHA) levels in rat brain. Importantly, 17-hydroxy-DHA has been shown to exert anti-inflammatory properties under different experimental conditions.…”

Section: ■ Effects Of Lithium On Inflammatory Mediatorsmentioning

confidence: 89%

Effects of Lithium on Inflammation

Nassar

Azab

2014

ACS Chem. Neurosci.

166

117

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Lithium is an effective medication for the treatment of bipolar affective disorder. Accumulating evidence suggests that inflammation plays a role in the pathogenesis of bipolar disorder and that lithium has anti-inflammatory effects that may contribute to its therapeutic efficacy. This article summarizes the studies which examined the effects of lithium on pro-and anti-inflammatory mediators. Some of the summarized data suggest that lithium exerts antiinflammatory effects (e.g., suppression of cyclooxygenase-2 expression, inhibition of interleukin (IL)-1β and tumor necrosis factor-α production, and enhancement of IL-2 and IL-10 synthesis). Nevertheless, there is a large body of data which indicates that under certain experimental conditions lithium also exhibits pro-inflammatory properties (e.g., induction of IL-4, IL-6 and other pro-inflammatory cytokines synthesis). The reviewed studies utilized various experimental model systems, and it is thus difficult to draw an unequivocal conclusion regarding the effect of lithium on specific inflammatory mediators.

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Section: ■ Effects Of Lithium On Inflammatory Mediatorsmentioning

confidence: 89%

Effects of Lithium on Inflammation

Nassar

Azab

2014

ACS Chem. Neurosci.

166

117

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“…Chronic NMDA independently promotes neuronal death and pro- and anti-apoptotic factors in rat brain [42]. An association between increased expression of AA cascade enzymes and neurocognitive impairments/neurodegeneration has been suggested for Alzheimer disease and vascular dementia [43], [45].…”

Section: Discussionmentioning

confidence: 99%

Neuropathological Responses to Chronic NMDA in Rats Are Worsened by Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil Supplementation

et al. 2014

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BackgroundDietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.MethodsMale rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured.ResultsCompared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA2 activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA2 activity or protein compared with the adequate group. sPLA2 expression was unchanged in the three conditions, whereas iPLA2 expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups.ConclusionsN-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content.

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“…In a rat model of neuroinflammation, six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS), at a rate of 0.5 ng/h, increased whole brain activities of cPLA 2 -IV and sPLA 2 , turnover rates of AA in brain phospholipids, and brain concentrations of unesterified AA and of its PGE 2 , TXB 2 and leukotriene B 4 metabolites, without altering DHA metabolism (Basselin et al, 2007c; Basselin et al, 2010a; Basselin et al, 2011a; Rosenberger et al, 2004; Rosenberger et al, 2010). Longer infusion of LPS caused behavioral changes and microglial activation, which could be reduced by ibuprofen (Richardson et al, 2005).…”

Section: Animal Models Of Neuroinflammation and Effects Of Lithiummentioning

confidence: 99%

“…Feeding LiCl to rats for 6 weeks, to produce plasma and brain lithium concentrations therapeutically relevant to BD, prevented many of the LPS-induced changes (Basselin et al, 2007c; Basselin et al, 2010a). In rats on a control LiCl-free diet, LPS compared with artificial cerebrospinal fluid (aCSF) infusion increased k* significantly in 28 regions, as well as brain cPLA 2 -IV activity and PGE 2 and TXB 2 concentrations; the LiCl diet prevented these increments (Figure 5).…”

Section: Animal Models Of Neuroinflammation and Effects Of Lithiummentioning

confidence: 99%

Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans

Basselin

Ramadan

Rapoport

2012

Brain Research Bulletin

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The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics.

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Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation

Cited by 49 publications

References 64 publications

Effects of Lithium on Inflammation

Effects of Lithium on Inflammation

Neuropathological Responses to Chronic NMDA in Rats Are Worsened by Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil Supplementation

Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans

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