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

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.

[The influence of antisecretory agents on the antral gastric mucosa in patients with duodenal ulcer].

Changes in the antral gastric mucosa of patients with doudenal ulcer after a long-term administration of antisecretory agents were studied. The subjects were five patients with a different duration of the disease. The methods applied included light and electron microscopy of tissue samplings taken from the antral part of the stomach during the periods of exacerbation and remission.

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

The extent to which the adult brain can derive some of its arachidonic acid (AA) through internalized synthesis from linoleic acid (LA) is uncertain. Thus, we determined for plasma-derived LA in vivo rates for brain incorporation, beta-oxidation, and conversion to AA. Adult male unanesthetized rats, reared on a diet enriched in LA but low in AA, were infused intravenously for 5 min with [1-(14)C]LA.

[Respiratory test in a gastroenterologist's practice].

The authors describe the principle of the respiratory test, review possibilities it provides in diagnostics, screening, and evaluation of the results of treatment of alimentary tract diseases, as well as its advantages over other diagnostic methods.

[Geomagnetic pulsations and myocardial infarctions].

Aim: To clarify the role of geomagnetic micropulsations Pc1 (0.2-5s) in the range of the basic heart rate in an increase in the number of myocardial infarctions (MI) and sudden death (SD).

Material And Methods: MI incidence rate in Moscow for 1979-1981, SD incidence rate in Bolgaria for 15 years for rural and urban population and data on micropulsations Pc1 were analysed.

RETRACTED: Chronic administration of carbamazepine down-regulates AP-2 DNA-binding activity and AP-2alpha protein expression in rat frontal cortex.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

Measuring brain uptake and incorporation into brain phosphatidylinositol of plasma myo-[2H6]inositol in unanesthetized rats: an approach to estimate in vivo brain phosphatidylinositol turnover.

The in vivo rate of turnover of phosphatidylinositol (PtdIns) in brain is not known. In brain, certain receptor-mediated signal transduction involves metabolism of PtdIns and a method to measure its turnover in awake animals is useful in studying the effect of lithium and other therapeutic agents. In a method described here, rats were infused subcutaneously with myo-[2H6]inositol (Ins*) using an osmotic pump and, at 1 and 8 weeks, concentrations of free myo-inositol (Ins) and Ins* in plasma and brain were measured by GC-MS (chemical ionization).

Regional network of magnetic resonance imaging gray matter volume in healthy aging.

Healthy aging has been associated with brain volume reductions preferentially affecting the frontal cortex, but also involving other regions. We used a network model of regional covariance, the Scaled Subprofile Model, with magnetic resonance imaging voxel-based morphometry to identify the regional distribution of gray matter associated with aging in 26 healthy adults, 22-77 years old. Scaled Subprofile Model analysis identified a pattern that was highly correlated with age (R2=0.

Chronic lithium chloride administration to rats elevates glucose metabolism in wide areas of brain, while potentiating negative effects on metabolism of dopamine D2-like receptor stimulation.

Rationale And Objectives: The regional cerebral metabolic rate for glucose (rCMRglc) can be imaged in vivo as a marker of brain functional activity. The effects of chronic lithium administration on baseline values of rCMRglc and values in response to administration of dopamine D2-like receptor agonists have not been examined in humans or rats. Knowing these effects may elucidate and localize the therapeutic action of lithium in bipolar disorder.

Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex.

Background: G-protein receptor kinases (GRKs) are a family of serine/threonine kinases involved in the homologous desensitization of agonist activated G-protein coupled receptors (GPCRs). G-protein coupled receptor supersensitivity, possibly as a result of decreased GRK, has been suggested in affective disorders.

Methods: We used immunobloting to determine if chronic, therapeutically relevant doses of lithium (Li+), carbamazepine (CBZ), and valproate (VPA), would increase GRK2/3 protein levels in rat frontal cortex.

Low liver conversion rate of alpha-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet.

We quantified the rates of incorporation of alpha-linolenic acid (alpha-LNA; 18:3n-3) into "stable" lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of alpha-LNA to docosahexaenoic acid (DHA; 22: 6n-3) in the liver of awake male rats on a high-DHA-containing diet after a 5-min intravenous infusion of [1-(14)C]alpha-LNA. At 5 min, 72.7% of liver radioactivity (excluding unesterified fatty acid radioactivity) was in stable lipids, with the remainder in the aqueous compartment.

Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A2 in rat frontal cortex.

Chronic lithium and carbamazepine, which are effective against mania in bipolar disorder, decrease the activity of cytosolic phospholipase A(2) (cPLA(2)) and the turnover rate of arachidonic acid in phospholipids in rat brain. Assuming that stages of bipolar disorder are related to brain arachidonic acid metabolism, we hypothesized that drugs effective in depression would increase cPLA(2) activity. To test this hypothesis, adult male CDF-344 rats were administered fluoxetine (10 mg/kg intraperitoneally (i.

Chronic fluoxetine upregulates arachidonic acid incorporation into the brain of unanesthetized rats.

Serotonergic 5-HT(2A/2C) receptors can be coupled to phospholipase A(2) (PLA(2)) activation to release the second messenger, arachidonic acid (AA), from membrane phospholipids. We wished to see if this signaling process in rat brain would be altered by chronic administration followed by 3days of washout of the selective serotonin reuptake inhibitor, fluoxetine. We injected [(3)H]AA intravenously in unanesthetized rats and used quantitative autoradiography to determine the incorporation coefficient k() for AA (regional brain radioactivity/integrated plasma radioactivity), a marker of PLA(2) activation, in each of 86 brain regions.

D-Amphetamine stimulates D2 dopamine receptor-mediated brain signaling involving arachidonic acid in unanesthetized rats.

In rat brain, dopaminergic D(2)-like but not D(1)-like receptors can be coupled to phospholipase A(2) (PLA(2)) activation, to release the second messenger, arachidonic acid (AA, 20:4n-6), from membrane phospholipids. In this study, we hypothesized that D-amphetamine, a dopamine-releasing agent, could initiate such AA signaling. The incorporation coefficient, k* (brain radioactivity/integrated plasma radioactivity) for AA, a marker of the signal, was determined in 62 brain regions of unanesthetized rats that were administered i.

Immediate no-flow ischemia decreases rat heart nonesterified fatty acid and increases acyl-CoA species concentrations.

Tissues changes in FA metabolism can occur quite rapidly in response to ischemia and may require immediate microwave fixation to determine basal concentrations. The present study aimed to quantify the effects of immediate no-flow ischemia on concentrations of individual nonesterified FA (NEFA) and acyl-CoA species in the rat heart. Male CDF 344 rats were anesthetized and decapitated either 5 min prior to being microwaved (5.

Selective remodeling of cardiolipin fatty acids in the aged rat heart.

Background: The heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Whether or not aging alters the composition of cardiolipin acyl chains is controversial. We therefore measured the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old rats that consumed one diet, adequate in fatty acids for the duration of their life.

Resting and arecoline-stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase-2 knockout mouse.

Abstract Studies were performed to determine if cyclooxygenase (COX)-2 regulates muscarinic receptor-initiated signaling involving brain phospholipase A2 (PLA2) activation and arachidonic acid (AA; 20 : 4n-6) release. AA incorporation coefficients, k* (brain [1-14C]AA radioactivity/integrated plasma radioactivity), representing this signaling, were measured following the intravenous injection of [1-14C]AA using quantitative autoradiography, in each of 81 brain regions in unanesthetized COX-2 knockout (COX-2(-/-)) and wild-type (COX-2(+/+)) mice. Mice were administered arecoline (30 mg/kg i.

Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder.

Rationale: Several drugs used to treat bipolar disorder (lithium and carbamazepine), when administered chronically to rats, reduce the turnover of arachidonic acid, but not docosahexaenoic acid, in brain phospholipids by decreasing the activity of an arachidonic acid-selective phospholipase A(2). Although chronic valproic acid produces similar effects on brain arachidonic acid and docosahexaenoic acid turnover, it does not alter phospholipase A(2) activity, suggesting that it targets a different enzyme in the turnover pathway.

Materials And Methods/results: By isolating rat brain microsomal long-chain fatty acyl-CoA synthetases (Acsl), we show in vitro that valproic acid is a non-competitive inhibitor of Acsl, as it reduces the maximal velocity of the reaction without changing the affinity of the substrate for the enzyme.

Chronic lithium chloride administration attenuates brain NMDA receptor-initiated signaling via arachidonic acid in unanesthetized rats.

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 phospholipid, we administered subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl diet. We used quantitative autoradiography following the intravenous injection of radiolabeled AA to measure regional brain incorporation coefficients k* for AA, which reflect receptor-mediated activation of PLA2.

Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine.

Objective: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system.

Method: In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest.

One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats.

Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged.

Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder.

Background: The basis for carbamazepine's efficacy in treating bipolar disorder is not agreed on. One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamazepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids.

Methods: To assess whether it targets brain AA kinetics, we administered carbamazepine (25 mg/kg/day, IP) to rats for 30 days and then determined its effect compared with that of vehicle on incorporation and turnover rates of AA and docosahexaenoic acid (DHA) in brain phospholipids.

Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat.

Interest in the potential therapeutic utility of topiramate for treating bipolar disorder was stimulated by published reports of investigator-initiated open label clinical studies. Because chronic lithium, carbamazepine and valproate decrease the turnover of arachidonic acid (AA) but not docosahexaenoic acid (DHA) in brain phospholipids of the awake rat, we tested if topiramate would produce similar results. Rats received either topiramate (20 mg/kg twice per day) or vehicle for 14 days and then while unanesthetized were infused intravenously with either [1-(14)C] AA or [1-(14)C] DHA for 5 min while blood was collected from the femoral artery at fixed times.