The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms?

Rationale: A sensitized dopamine system may be linked to the genesis of psychotic symptoms in schizophrenia. Following withdrawal from amphetamine exposures, psychotic-like traits have been robustly demonstrated, but the presence of cognitive/mnemonic deficits remains uncertain. Methods: Adult male Lewis and Fischer rats, differing in cognitive performance, were exposed intermittently to escalating doses of amphetamine over 5weeks. This was effective in producing behavioral sensitization to a subsequent amphetamine challenge. Following 27days of drug withdrawal, the animals were assessed in Pavlovian conditioning, object recognition, and spatial working memory. In addition, prepulse inhibition (PPI), spontaneous motor activity, and anxiety-like behavior were measured. Results: Amphetamine pretreatment induced behavioral sensitization in both rat strains similarly. Working memory was enhanced in Fischer but not Lewis rats following withdrawal. Spontaneous novel object preference was enhanced in sensitized Fischer rats, but was impaired in sensitized Lewis rats, thus effectively reversing the strain difference in non-sensitized controls. In contrast, Pavlovian fear conditioning remained unaffected and so were anxiety-like behavior, open field activity, and PPI. Conclusion: The face validity of the amphetamine withdrawal model for cognitive deficits was limited to the object recognition memory impairment observed in sensitized Lewis rats. Yet, the possibility that enhancing dopaminergic neurotransmission may facilitate object recognition and spatial working memory performance was demonstrated in sensitized Fischer rats. Identification of the mechanisms underlying such strain-dependent effects would be instrumental in the further specifications of the construct validity, and therefore the limitations and potential of the amphetamine sensitization model of schizophreni

Baseline prepulse inhibition expression predicts the propensity of developing sensitization to the motor stimulant effects of amphetamine in C57BL/6 mice

Rationale: The startle reflex to a sudden intense acoustic pulse stimulus is attenuated if the pulse is shortly preceded by a weak prepulse stimulus. This represents a form of sensory gating, known as prepulse inhibition (PPI), observable across species. PPI is modulated by dopamine and readily disrupted by acute amphetamine. Prior repeated exposures to amphetamine also disrupt PPI even when the drug is not present during test, suggesting that a sensitized mesolimbic dopamine system—inducible even by a single exposure to amphetamine—might be responsible. However, this causative link has been challenged by inconsistent efficacy between different amphetamine pre-treatment regimes, which all robustly sensitize the behavioral response to amphetamine. Methods: Here, the presence of such a link in reverse was tested by comparing the propensity to develop amphetamine sensitization between high- and low-PPI expressing individuals identified within a homogeneous cohort of C57BL/6 mice. Comparison of dopamine content including its metabolites was performed separately in drug naïve mice by post-mortem HPLC. Results: Behavioral sensitization was substantially stronger in the low-PPI group compared with the high-PPI group, while the magnitude of their response to the first amphetamine challenge was similar. Dopamine content within the nucleus accumbens and medial prefrontal cortex was significantly higher in low-PPI relative to high-PPI mice. Conclusion: Individuals with weak sensory gating characterized by low basal PPI expression may be more susceptible to the development of dopamine sensitization and therefore at greater risk of developing schizophrenia. Conversely, high baseline expression might predict a resistance to dopaminergic sensitizatio

Similar Hemoglobin Mass Response in Hypobaric and Normobaric Hypoxia in Athletes

Purpose: To compare hemoglobin mass (Hbmass) changes during an 18-day live high-train low (LHTL) altitude training camp in normobaric hypoxia (NH) and hypobaric hypoxia (HH). Methods: Twenty-eight well-trained male triathletes were split into three groups (NH: n = 10, HH: n = 11, control (CON): n = 7) and participated in an 18-day LHTL camp. NH and HH slept at 2250 m while CON slept and all groups trained at altitudes 0.08) and remained unchanged in CON (+0.2%, P = 0.89). Conclusion: HH and NH evoked similar Hbmass increases for the same hypoxic dose and after 18-day LHTL. The wide variability in individual Hbmass responses in HH and NH emphasize the importance of individual Hbmass evaluation of altitude training.This study was financially supported by the Federal Office of Sport (FOSPO; Switzerland) and by the Ministère des Sports, de la Jeunesse, de l’Education Populaire et de la Vie Associative (MSJEPVA)/Institut National du Sport, de l’Expertise et de la Performance (INSEP, France)

Individual hemoglobin mass response to normobaric and hypobaric “live high–train low”: A one-year crossover study

The purpose of this research was to compare individual hemoglobin mass (Hbmass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-day LHTL training camps in either HH or NH. All athletes slept at 2,250 meters and trained at altitudes <1,200 meters. Hbmass was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre) and immediately after (post) each 18-day training camp. Hbmass increased similarly in HH (916–957 g, 4.5 ± 2.2%, P < 0.001) and in NH (918–953 g, 3.8 ± 2.6%, P < 0.001). Hbmass changes did not differ between HH and NH (P = 0.42). There was substantial interindividual variability among subjects to both interventions (i.e., individual responsiveness or the individual variation in the response to an intervention free of technical noise): 0.9% in HH and 1.7% in NH. However, a correlation between intraindividual ΔHbmass changes (%) in HH and in NH (r = 0.52, P = 0.048) was observed. HH and NH evoked similar mean Hbmass increases following LHTL. Among the mean Hbmass changes, there was a notable variation in individual Hbmass response that tended to be reproducible.This study was financially supported by the Federal Office of Sport (Switzerland) and by the Ministère des Sports, de la Jeunesse, de l’Education Populaire et de la Vie Associative/Institut National du Sport, de l’Expertise et de la Performance (France)

Correction: Comparison of “Live High-Train Low” in Normobaric versus Hypobaric Hypoxia

[This corrects the article DOI: 10.1371/journal.pone.0114418.]

Interactions between Bifidobacterium and Bacteroides and human milk oligosaccharides and their associations with infant cognition

While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of Bacteroides and Bifidobacterium genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9–12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of Bacteroides and Bifidobacterium species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With Bacteroides species, we observed significant associations with motor functions, while Bif. catenulatum showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of p = 0.012) and in interaction with LNFP-I (value of p = 0.007). Additionally, 3-FL showed a positive association with gross motor (p = 0.027) and visual reception (p = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for Bifidobacterium species and LNT [breve (p = 0.011) and longum (p = 0.022)], and positive associations for expressive language with 3′-SL and Bif. bifidum (p = 0.01), 6′-SL and B. fragilis (p = 0.019), and LNFP-I and Bif. kashiwanohense (p = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and Bacteroides and Bifidobacterium species reveal different candidate pathways through which HMOs, Bifidobacterium and Bacteroides species potentially interact to impact cognitive development in infancy

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Joint analyses of human milk fatty acids, phospholipids, and choline in association with cognition and temperament traits during the first 6 months of life

Early dietary exposure via human milk nutrients offers a window of opportunity to support cognitive and temperament development. While several studies have focused on associations of few pre-selected human milk nutrients with cognition and temperament, it is highly plausible that human milk nutrients synergistically and jointly support cognitive and behavioral development in early life. We aimed to discern the combined associations of three major classes of human milk nutrients with cognition and temperament during the first 6 months of life when human milk is the primary source of an infant’s nutrition and explore whether there were persistent effects up to 18 months old. The Mullen Scales of Early Learning and Infant Behavior Questionnaires—Revised were used to assess cognition and temperament, respectively, of 54 exclusively/predominantly breastfed infants in the first 6 months of life, whose follow-ups were conducted at 6–9, 9–12, and 12–18 months old. Human milk samples were obtained from the mothers of the participants at less than 6 months of age and analyzed for fatty acids [total monounsaturated fatty acids, polyunsaturated fatty acid, total saturated fatty acid (TSFA), arachidonic acid (ARA), docosahexaenoic acid (DHA), ARA/DHA, omega-6/omega-3 polyunsaturated fatty acids ratio (n-6/n-3)], phospholipids [phosphatidylcholine, phosphatidylethanolamine (PE), phosphatidylinositol (PI), sphingomyelin], and choline [free choline, phosphocholine (PCho), glycerophosphocholine]. Feature selection was performed to select nutrients associated with cognition and temperament. The combined effects of selected nutrients were analyzed using multiple regression. A positive association between the arachidonic acid (ARA) and surgency was observed (p = 0.024). A significant effect of DHA, n-6/n-3, PE, and TSFA concentrations on receptive language (R2 = 0.39, p = 0.025) and the elevated ARA, PCho, and PI with increased surgency (R2 = 0.43, p = 0.003) was identified, suggesting that DHA and ARA may have distinct roles for temperament and language functions. Furthermore, the exploratory association analyses suggest that the effects of human milk nutrients on R.L. and surgency may persist beyond the first 6 months of life, particularly surgency at 12–18 months (p = 0.002). Our study highlighted that various human milk nutrients work together to support the development of cognition and temperament traits during early infancy

Entwicklung von Rückbau- und Recyclingstandards für Rotorblätter : Abschlussbericht [Kurztitel: Aufbereitung von Rotorblättern]

Als Ergebnis der breiten politischen Befürwortung für die Energiewende und des stetig wachsenden Bestands an Windenergieanlagen (WEA) in Deutschland und Europa gewinnen Fragen der Wartung, Laufzeitverlängerung sowie des Anlagenrückbaus und Recyclings an Bedeutung. Eine besondere Herausforderung stellt dabei das Rotorblattrecycling mit ihren glasfaserverstärkten (GFK) und carbonfaserverstärkten (CFK) Anlagenteilen dar. Die für diese Materialien existierenden Recyclingprozesse haben sich noch nicht durchgesetzt und der Wiedereinsatz der recyclierten Materialien ist in der Breite nicht etabliert. Weiterhin mangelt es an Standards für die Demontage und werkstoffliche Aufbereitung dieser Materialien. Zentraler Forschungsgegenstand war die Entwicklung von Standards für eine möglichst hochwertige und gleichzeitig wirtschaftlich zumutbare Aufbereitungs- und Behandlungsstrategie für Rotorblätter. Ausgehend von den zu erwartenden Abfallmengen und - arten und des speziellen Aufbaus und der Zusammensetzung der verschiedenen Rotorblätter wurde ein vollständiges und schlüssiges Konzept für deren Wartungen, Reparatur, Demontage, Vorzerkleinerung und Aufbereitung erarbeitet. Darauf basierend wurde die Organisationsverantwortung aus rechtlicher Sicht geprüft und mögliche erforderlicher, ergänzender materiell-rechtlicher Vorgaben vorgeschlagen. Auch Elemente der abfallwirtschaftlichen Produktverantwortung wurden auf Zweckmäßigkeit geprüft und bewertet. Die Studie beschreibt damit ein erstes umfassendes technisches, rechtliches und organisatorisches Recyclingkonzept für Rotorblätter