Chronic carbamazepine selectively downregulates cytosolic phospholipase A2 expression and cyclooxygenase activity in rat brain

Ghelardoni, Sandra; Tomita, York; Bell, Jane M.; Rapoport, Stanley I.; Bosetti, Francesca

doi:10.1016/j.biopsych.2004.05.012

Cited by 94 publications

(109 citation statements)

References 38 publications

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“…56 Data were expressed as the level of the target gene (BDNF) in the n-PUFA-deprived animals normalized to the endogenous control (b-globulin) and relative to the n-3 PUFA-adequate animals (calibrator), as previously described. 57 All experiments were carried out twice in triplicate with six independent samples.…”

Section: Dha Quantificationmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

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Section: Dha Quantificationmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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“…For example, chronic LiCl like chronic CBZ blocked quinpirole-induced increments in k* for AA (we have not as yet examined lithium's ability to block the PGE 2 increment following quinpirole). Both chronic LiCl and CBZ reduced AA turnover in rat brain phospholipids, brain mRNA, protein and activity levels of cPLA 2 , and the DNAbinding capacity and protein level of a cPLA 2 transcription factor, activator protein-2 [11,19,27,42,43,45]. These observations, plus clinical data that dopaminergic neurotransmission is disturbed in bipolar disorder [13,28,31], and that dopamine receptor antagonists can be therapeutic whereas drugs that stimulate dopamine synthesis, bind to dopamine receptors or reduce dopamine reuptake often precipitate mania (see "Introduction"), suggest that mood stabilizers are therapeutic in bipolar disorder in part by suppressing excessive D 2 -like receptor signaling involving AA.…”

Section: Discussionmentioning

confidence: 98%

“…CBZ also could have altered G-protein receptor kinase translocation from cytosol to cell membrane, and thus densitiztion of D 2 -like receptors [24]. CBZ's ability to reduce rat brain cPLA 2 transcription and COX activity also could have contributed to the reduced signaling, associated with reduced basal PGE 2 and TXB 2 concentrations and reduced quinpiroleinduced changes in these concentrations [8,27]. PGE 2 and TXB 2 are converted preferentially from AA by COX-2 and COX-1, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…CBZ-treated rats received 25 mg/kg intraperitoneally once daily for 30 days (Sigma-Aldrich). The CBZ was dissolved in a 50:50 (v/v) dimethyl sulfoxide (DMSO, ≥99.9% Sigma-Aldrich): saline (0.9% NaCl, Hospira Inc., Lake Forest, IL, USA) mixture and kept at 37°C as described previously [2,11,27]. A control group received the same volume of DMSO:saline (vehicle) under parallel conditions.…”

Section: Drugsmentioning

confidence: 99%

“…vehicle or CBZ 25 mg/kg, then administered saline (control) or quinpirole (1.0 mg/kg i.v.). The CBZ regimen produces a plasma CBZ concentration of 54 μM, at the high end found in CBZ-treated bipolar patients (51 μM), and decreases AA turnover in brain phospholipids and the brain PGE 2 concentration [2,11,18,27]. The quinpirole dose increases k* for AA significantly in brain dopaminergic circuits [5,15].…”

Section: Introductionmentioning

confidence: 99%

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Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

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Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D 2 -like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D 2 -like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E 2 (PGE 2 ), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE 2 concentration. Affected regions belong to dopaminergic circuits and have high D 2 -like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE 2 . These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D 2 -like receptors, and that this signaling is upregulated in bipolar disorder.

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Interactions between neural membrane glycerophospholipid and sphingolipid mediators: A recipe for neural cell survival or suicide

Farooqui

Horrocks

Farooqui

2007

J of Neuroscience Research

107

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The neural membranes contain phospholipids, sphingolipids, cholesterol, and proteins. Glycerophospholipids and sphingolipids are precursors for lipid mediators involved in signal transduction processes. Degradation of glycerophospholipids by phospholipase A(2) (PLA(2)) generates arachidonic acid (AA) and docosahexaenoic acids (DHA). Arachidonic acid is metabolized to eicosanoids and DHA is metabolized to docosanoids. The catabolism of glycosphingolipids generates ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These metabolites modulate PLA(2) activity. Arachidonic acid, a product derived from glycerophospholipid catabolism by PLA(2), modulates sphingomyelinase (SMase), the enzyme that generates ceramide and phosphocholine. Furthermore, sphingosine 1-phosphate modulates cyclooxygenase, an enzyme responsible for eicosanoid production in brain. This suggests that an interplay and cross talk occurs between lipid mediators of glycerophospholipid and glycosphingolipid metabolism in brain tissue. This interplay between metabolites of glycerophospholipid and sphingolipid metabolism may play an important role in initiation and maintenance of oxidative stress associated with neurologic disorders as well as in neural cell proliferation, differentiation, and apoptosis. Recent studies indicate that PLA(2) and SMase inhibitors can be used as neuroprotective and anti-apoptotic agents. Development of novel inhibitors of PLA(2) and SMase may be useful for the treatment of oxidative stress, and apoptosis associated with neurologic disorders such as stroke, Alzheimer disease, Parkinson disease, and head and spinal cord injuries.

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Chronic carbamazepine selectively downregulates cytosolic phospholipase A2 expression and cyclooxygenase activity in rat brain

Cited by 94 publications

References 38 publications

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Interactions between neural membrane glycerophospholipid and sphingolipid mediators: A recipe for neural cell survival or suicide

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