Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females

Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20–31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants’ menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed.     

Effects of acute tryptophan depletion on brain serotonin function and concentrations of dopamine and norepinephrine in C57BL/6J and BALB/cJ mice

Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP-) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain-specific effect of ATD Moja-De on anxiety-like behavior.     

Nitrous oxide (N<Subscript>2</Subscript>O) and subsequent open-label SSRI treatment of adolescents with depression (NOTAD): study protocol for a randomised controlled trial

Background

The first line of pharmacological treatment for severe depressive disorders in young people is selective serotonin reuptake inhibitors (SSRIs). However, beneficial clinical effects are rarely observed before several weeks into treatment. Nitrous oxide (N₂O) has a long-standing safety record for pain relief and has been used in adults and young people. In adults with severe treatment-resistant depression, a single dose of N₂O had significant antidepressant effects, with maximum antidepressant effects observed 24 h after administration. However, the antidepressant effects of N₂O have never been investigated in adolescents with a confirmed diagnosis of depression in a prospective trial. The aims of this study are to (1) investigate whether a single inhaled N₂O administration leads to antidepressant effects in adolescents with depression at 24 h, (2) determine whether combined N₂O and SSRI administration (commenced after N₂O intervention) provides a clinically significant improvement in mood over and above the benefits from SSRI administration alone, and, (3) investigate whether the effect seen following N₂O administration can be used as a predictor of SSRI treatment response.

Methods/design

In this study, we will use a single-blind, randomised, placebo-controlled design. Patients aged between 12 and 17 years with major depressive disorder will be recruited. This study will consist of two phases: phase A and phase B. During phase A, participants will be randomised to receive either inhaled N₂O or placebo (air) for 1 h. In phase B, participants will receive open-label pharmacological treatment with the SSRI fluoxetine and will be followed over a 12-week period. Participants will undertake mood assessments at 2 and 24 h after N₂O or placebo administration (phase A) and weekly during the 12-week follow up in phase B.

Discussion

We expect an antidepressant effect from a single dose of inhaled N₂O compared with placebo at 24 h after administration. Additionally, we expect that subjects treated with N₂O will also show greater improvements than the placebo group after 6 and 12 weeks into fluoxetine treatment because of potential additive antidepressant effects. Such findings would be of clinical importance because currently children and adolescents often do not experience any symptom alleviation for several weeks following the initiation of SSRIs.

Trial registration

Australian and New Zealand Clinical Trials Registry, ACTRN12616001568404. Registered on 14 November 2016.

     

Properties of microtubule sliding disintegration in isolated tetrahymena cilia

Properties of the sliding disintegration response of demembranated tetrahymena cilia have been studied by measuring the spectrophotomeric response or turbidity of cilia suspensions at a wavelength of 350 nm relative to changes in the dynein substrate (MgATP(2-)) concentration. The maximum decrease in turbidity occurs in 20 muM ATP, and 90 percent of the decrease occurs in approximately 5.9 s. At lower ATP concentrations (1-20 muM), both the velocity and magnitude of the turbidity decreases are proportional to ATP concentration. The velocity data for 20 muM ATP permit construction of a reaction velocity curve suggesting that changes in turbidity are directly proportional to the extent and velocity of disintegration. At ATP concentrations more than 20 muM (50muM to 5mM), both velocity and magnitude of the turbidimetric response are reduced by approximately 50 percent. This apparent inhibition results in a biphasic response curve that may be related to activation of residual shear resistance or regulatory components at the higher ATP concentrations. The inhibitory effects of elevated ATP can be eliminated by mild trypsin proteolysis, whereupon the reaction goes to completion at any ATP concentration. The turbidimetric responses of the axoneme-substrate suspensions are consistent with the extent and type of axoneme disintegration revealed by electron microscope examination of the various suspensions, suggesting that the turbidimetric assay may prove to be a reliable means for assessing the state of axoneme integrity.     

Production of Poly(3-hydroxybutyrate) from waste potato starch

There has been a considerable interest in using low cost carbon substrates for the production of Poly(3-hydroxybutyrate) (PHB). We have shown that saccharified waste potato starch can be used as a viable alternative carbon source in high cell density PHB production. Using Ralstonia eutropha NCIMB 11599 with phosphate limitation, 179 g/l biomass, 94 g/l PHB, Y(biomass/starch) = 0.46 g/g, Y(PHB/starch) = 0.22 g/g, and PHB productivity = 1.47 g/(l*h) were achieved. Residual maltose accumulated in the fed-batch reactor but caused no noticeable inhibition. Performance with saccharified starch was virtually identical to that with glucose.     

Characterization of the opsonic and monocyte adherence functions of the specific fibronectin fragment that enhances phagocytosis of particulate activators

The functional opsonic and monocyte adherence domains within the 180,000 m.w. opsonic fibronectin fragment (180K-opFnf) that selectively augments human monocyte phagocytosis of particulate activators of the alternative complement pathway were analyzed with Fab fragments of monoclonal anti-fibronectin antibodies BC7, CE9, BD4, AB3, and CPG1, and with fragments of intact human plasma fibronectin derived by cathepsin cleavage and isolated by affinity chromatography. Monoclonals AB3 and CPG1, which recognize epitopes within 40,000 daltons of the carboxy terminus of intact fibronectin, and the cathepsin D-derived, disulfide-linked fragments that contain these epitopes each inhibited the opsonic function of 180K-opFnf. Monoclonals AB3 and CPG1 inhibited monocyte ingestion of rabbit erythrocytes (Er) by 60 and 50%, respectively, when 180K-opFnf was pretreated with 20 micrograms of these monoclonals, but neither monoclonal affected the enhanced monocyte ingestion of Er pretreated with the fibronectin fragment. The pretreatment of Er with 5 micrograms and 40 micrograms of the disulfide-linked, cathepsin D derivatives isolated from high and low affinity heparin fractions, respectively, inhibited the proportion of ingesting monocytes by 60%, but these types of fragments had little effect when concurrently incubated with the opsonic fragment and Er. Monoclonals CE9 and BD4, which recognize epitopes located adjacent to or within the cell-adhesive domain of intact fibronectin, respectively, inhibited the monocyte adherence function of 180K-opFnf, as evidence by their comparable inhibitory effects when present before or after Er were opsonized with 180K-opFnf. When 20 micrograms of monoclonals CE9 and BD4 were each introduced before and after Er were opsonized with 180K-opFnf, monocyte ingestion was inhibited by 60 and 65% and by 51 and 60%, respectively. At 42 micrograms, cathepsin D-derived, non-gelatin-binding, low affinity heparin fragments that contained both BD4 and CE9 determinants or only the BD4 determinant inhibited monocyte ingestion by 53 and 74%, respectively, when concurrently incubated with 180K-opFnf and target Er, but were without effect when used to pretreat Er before the addition of 180K-opFnf. Thus, the inhibitory effects produced by monoclonals AB3 and CPG1 and by cathepsin D-derived, disulfide-linked fragments containing their corresponding epitopes demonstrated that the opsonic domain within 180K-opFnf is immunologically similar to regions within the carboxy terminus of intact plasma fibronectin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Attentional performance, age and scholastic achievement in healthy children

Background

Attentional processes in children play a critical role in daily school demands and accomplishments. Studies on the association of attentional processes with school achievement and age in healthy school children are scarce. The aim of the present study was to identify correlations between dimensions of attentional performance, scholastic achievement and age.

Methodology/Principal Findings

An extensive testing battery was used to assess a wide range of attentional dimensions. A principal component analysis revealed three factors that are related to attentional performance (distractibility, lapses of attention, cognitive speed). Age was negatively associated with distractibility, lapses of attention and cognitive speed, indicating that distractibility and lapses of attention decreased with age in healthy children and resulted in lower cognitive speed.

Conclusions/Significance

Attentional processes in healthy children should be measured in relation to distractibility, lapses of attention and cognitive speed.