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Bipolar disorder (BD) is a major medical and social burden, whose cause, pathophysiology and treatment are not agreed on. It is characterized by recurrent periods of mania and depression (Bipolar I) or of hypomania and depression (Bipolar II). Its inheritance is polygenic, with evidence of a neurotransmission imbalance and disease progression. Patients(More)
Certain polymorphisms reduce serotonin (5-HT) reuptake transporter (5-HTT) function and increase susceptibility to psychiatric disorders. Heterozygous (5-HTT(+/-))-deficient mice, models for humans with these polymorphisms, have elevated brain 5-HT concentrations and behavioral abnormalities. As postsynaptic 5-HT(2A/2C) receptors are coupled to cytosolic(More)
BACKGROUND Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to(More)
The uptake of [(3)H]pentamidine into wild-type and drug-resistant strains of Leishmania mexicana was compared. Uptake was carrier mediated. Pentamidine-resistant parasites showed cross-resistance to other toxic diamidine derivatives. A substantial decrease in accumulation of the drug accompanied the resistance phenotype, although the apparent affinity for(More)
Neuroinflammation, caused by six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS), stimulates rat brain arachidonic acid (AA) metabolism. The molecular changes associated with increased AA metabolism are not clear. We examined effects of a six-day infusion of a low-dose (0.5 ng/h) and a high-dose (250 ng/h) of LPS on(More)
In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca(2+)-independent phospholipase A(2) (iPLA(2)), Ca(2+)-independent plasmalogen PLA(2) or secretory PLA(2 (sPLA2)), but not by Ca(2+)-dependent cytosolic PLA(2) (cPLA2), which selectively releases arachidonic acid (AA). Since glutamatergic NMDA(More)
BACKGROUND Dopamine transporter (DAT) homozygous knockout (DAT(-/-)) mice have a 10-fold higher extracellular (DA) concentration in the caudate-putamen and nucleus accumbens than do wildtype (DAT(+/+)) mice, but show reduced presynaptic DA synthesis and fewer postsynaptic D(2) receptors. One aspect of neurotransmission involves DA binding to postsynaptic(More)
Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether(More)
It has been proposed that lithium is effective in bipolar disorder (BD) by inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate receptors (NMDARs). To test this hypothesis and to see if the neurotransmission could involve the NMDAR-mediated activation of phospholipase A2 (PLA2), to release arachidonic acid (AA) from membrane(More)
We studied the effect of lithium chloride on dopaminergic neurotransmission via D2-like receptors coupled to phospholipase A2 (PLA2). In unanesthetized rats injected i.v. with radiolabeled arachidonic acid (AA, 20:4 n-6), regional PLA2 activation was imaged by measuring regional incorporation coefficients k* of AA (brain radioactivity divided by integrated(More)