Disambiguating the Effects of Social Instability Stress in Adolescence on Learning and Memory Tasks that Involve the Medial Prefrontal Cortex and Hippocampus

Exposure to chronic stress can alter the structure and function of brain regions involved in learning and memory, and these effects are typically long-lasting if the stress occurs during sensitive periods of development. Until recently, adolescence has received relatively little attention as a sensitive period of development, despite marked changes in behaviour, heightened reactivity to stressors, and cognitive and neural maturation. Therefore, the purpose of the present study was to investigate the long-term effects of chronic stress in adolescence on two spatial learning and memory tasks (Morris water maze and Spatial Object Location test) and on a working memory task (Delayed Alternation task). Male rats were randomly assigned to chronic social instability stress (SS; daily 1 hour isolation and subsequent change of cage partner between postnatal days 30 and 45) or to a no-stress control group (CTL). During acquisition learning in the Morris water maze task, SS rats demonstrated impaired long-term memory for the location of the hidden escape platform compared to CTL rats, although the impairment was only seen after the first day of training. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 minutes), but not after shorter delays (15 or 60 minutes) compared to CTL rats. On the Delayed Alternation task, which assessed working memory across delays ranging from 5 to 90 seconds, no group differences were observed. These results are partially in line with previous research that revealed adult impairment on spatial learning and memory tasks after exposure to chronic social instability stress in adolescence. The observed deficits, however, appear to be limited to long-term memory as no group differences were observed during brief periods of retention.

Effects of Cerebral Blood Flow and PETCO2 on Cognitive Function During Passive Heat Stress

This thesis tested whether cognitive performance during passive heat stress may be affected by changes in cerebrovascular variables as opposed to strictly thermally-induced changes. A pharmacological reduction in cerebral blood flow (CBF) using indomethacin along with a hypocapnia-induced CBF reduction during passive heat stress (Tre ~1.5°C above baseline) were used to investigate any cerebrovascular-mediated changes in cognitive performance. Repeated measures analysis of variance indicated that One-Touch Stockings of Cambridge (OTS) performance was not affected by a significant reduction in CBF during passive heat stress. More specifically, OTS accuracy measures did not change as a result of either a reduction in CBF or increasing passive heat stress. However, it was found that OTS response time indices improved with increasing passive heat stress independent of CBF changes. In conclusion, a significant reduction in CBF does not cause additional changes in performance of an executive functioning task during severe passive heat stress.

The effects of oxidative stress on the retinal structure and function

Des études antérieures ont démontré que le métabolisme de la rétine, son apport sanguin et sa consommation de l'oxygène sont plus élevés dans le noir (Riva C.E. et al. 1983, Wang L. et al. 1996, Tam B.M. and Moritz O.L. 2007). Les stimuli physiologiques jouent supposément un rôle important dans le développement des différents systèmes nerveux (Arthur W. Spira, David Parkinson 1991). La privation de la rétine de son stimulus physiologique, la lumière, est un moyen valable de démontrer la validité de ce concept. D'autres études ont affirmé que les injections de dichlorure de paraquat dans la cavité vitréenne causent une sévère rétinopathie (Rétinopathie induite par paraquat: RIP). Cette rétinopathie est provoquée par les dérivés réactifs de l'oxygène (DRO) générés par le paraquat (Cingolani C. et al. 2006, Lu L. et al. 2006). Le but de notre premier projet (''Dark rearing project'') était de déterminer si les conséquences nocives de l'hyperoxie postnatale chez les rats albinos SD pourraient être amoindries en élevant une portée de rats au noir. Nos résultats suggèrent qu'une augmentation du métabolisme de la rétine causée par la déprivation de lumière chez les ratons, pourrait protéger ou masquer certains effets néfastes de l'hyperoxie postnatale. Le but de notre deuxième étude (''Paraquat project'') était d'examiner les possibles points de similitude entre RIP et d'autres modèles de rétinopathies oxydatives étudiés présentement par notre équipe, à savoir: Rétinopathie induite par l'oxygène (RIO) et Rétinopathie induite par la lumière (RIL). Nos résultats suggèrent que l'injection de dichlorure de paraquat dans la cavité vitréenne cause des changements sévères de la fonction de la rétine, tandis que sa structure semble intacte. La sévérité de ces changements dépend inversement de la maturité de la rétine au moment de l'injection.

Effects of phosphorus and water stress on shoot and root growth and on mycorrhization of different pearl millet (Pennisetum glaucum (L.) R. Br.) varieties from West Africa

This research work aimed at investigating the physiological mechanisms of tolerance of pearl millet to low soil Phosphorus availability and drought under the Sahelian conditions.

Effects of host plant drought stress on the performance of the bird cherry-oat aphid, Rhopalosiphum padi (L.): a mechanistic analysis

1. The growth (increase in height and leaf number) of four grass species was reduced by a -0.5 MPa drought stress, but the performance of an associated herbivore, Rhopalosiphum padi (L.), was not affected consistently. The intrinsic rate of increase of R. padi was reduced by drought stress on three grass species, including Dactylis glomerata (L.), but was unaffected on Arrhenatherum elatius (L.). Therefore, there is no general relationship in the effect of plant drought on an insect herbivore, even among closely related host plant species. 2. Drought stress increased the quality of plant phloem sap, as indicated by increased sieve element osmotic pressure and essential amino acid concentrations. Thus, diet quality could not account for the reduced performance of R. padi under drought stress. The concentration of essential amino acids in the phloem of well-watered A. elatius was, however, lower than that of well-watered D. glomerata, correlating with the decreased performance of aphids on well-watered A. elatius. 3. There were no differences in aphid feeding duration between watering treatments or plant species but sap ingestion rates were reduced significantly under drought stress. 4. Using the measure of dietary amino acid concentrations and the estimate of sap ingestion, the essential amino acid flux through aphids was calculated. Compared with the flux through aphids feeding on well-watered D. glomerata, there was a reduction in aphids feeding on drought-stressed D. glomerata and drought-stressed A. elatius due to lower sap ingestion rates. The flux through aphids on well-watered A. elatius was also reduced due to low phloem essential amino acid concentrations. Thus, the performance of an aphid is correlated with the availability and accessibility of essential amino acids.

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study.

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

Differential regulation of Krüppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines

Krüppel-like transcription factors (Klfs) modulate fundamental cell processes. Cardiac myocytes are terminally-differentiated, but hypertrophy in response to stimuli such as endothelin-1. H2O2 or cytokines promote myocyte apoptosis. Microarray studies of neonatal rat myocytes identified several Klfs as endothelin-1-responsive genes. We used quantitative PCR for further analysis of Klf expression in neonatal rat myocytes. In response to endothelin-1, Klf2 mRNA expression was rapidly increased ( approximately 9-fold; 15-30 min) with later increases in expression of Klf4 and Klf6 ( approximately 5-fold; 30-60 min). All were regulated as immediate early genes (cycloheximide did not inhibit the increases in expression). Klf5 expression was increased at 1-2 h ( approximately 13-fold) as a second phase response (cycloheximide inhibited the increase). These increases were transient and attenuated by U0126. H2O2 increased expression of Klf2, Klf4 and Klf6, but interleukin-1beta or tumor necrosis factor alpha downregulated Klf2 expression with no effect on Klf4 or Klf6. Of the Klfs which repress transcription, endothelin-1 rapidly downregulated expression of Klf3, Klf11 and Klf15. The dynamic regulation of expression of multiple Klf family members in cardiac myocytes suggests that, as a family, they are actively involved in regulating phenotypic responses (hypertrophy and apoptosis) to extracellular stimuli.

Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective

There is strong evidence from animal studies that prenatal stress has different effects on male and female offspring. In general, although not always, prenatal stress increases anxiety, depression and stress responses, both hypothalamic–pituitary–adrenal and cardiovascular, in female offspring rather than in male. Males are more likely to show learning and memory deficits. There have been few studies so far in humans which differentiate effects of prenatal stress on male and female psychopathology. Some studies support the animal models, but the evidence is inconsistent. The mediating mechanisms for any sex specific effects are little understood, but there is evidence that placental function can differ depending on the sex of the fetus. We suggest that there may be an evolutionary reason for any sex differences in the long term effects of prenatal stress. In a stressful environment it may be adaptive for females, who are more likely to stay in one place and look after children, to be more vigilant, alert to danger and thus show more stress responsiveness. This can give rise to a more anxious or depressed phenotype. With males it may be more adaptive to go out and explore new environments, compete with other males, and be more aggressive. For this it may help to be less responsive to external stressors. More research is needed into sex differences in the effects of prenatal stress in humans, to test these ideas.

Evidence for interplay between genes and maternal stress in utero: monoamine oxidase A polymorphism moderates effects of life events during pregnancy on infant negative emotionality at 5 weeks

The low activity variant of the monoamine oxidase A (MAOA) functional promoter polymorphism, MAOA-LPR, in interaction with adverse environments (G × E) is associated with child and adult antisocial behaviour disorders. MAOA is expressed during foetal development so in utero G × E may influence early neurodevelopment. We tested the hypothesis that MAOA G × E during pregnancy predicts infant negative emotionality soon after birth. In an epidemiological longitudinal study starting in pregnancy, using a two stage stratified design, we ascertained MAOA-LPR status (low vs. high activity variants) from the saliva of 209 infants (104 boys and 105 girls), and examined predictions to observed infant negative emotionality at 5 weeks post-partum from life events during pregnancy. In analyses weighted to provide estimates for the general population, and including possible confounders for life events, there was an MAOA status by life events interaction (P = 0.017). There was also an interaction between MAOA status and neighbourhood deprivation (P = 0.028). Both interactions arose from a greater effect of increasing life events on negative emotionality in the MAOA-LPR low activity, compared with MAOA-LPR high activity infants. The study provides the first evidence of moderation by MAOA-LPR of the effect of the social environment in pregnancy on negative emotionality in infancy, an early risk for the development of child and adult antisocial behaviour disorders.

Effects of oxidative stress on the cardiac myocyte proteome: modifications to peroxiredoxins and small heat shock proteins

Endogenous oxidative stress is a likely cause of cardiac myocyte death in vivo. We examined the early (0-2 h) changes in the proteome of isolated cardiac myocytes from neonatal rats exposed to H2O2 (0.1 mM), focussing on proteins with apparent molecular masses of between 20 and 30 kDa. Proteins were separated by two-dimensional gel electrophoresis (2DGE), located by silver-staining and identified by mass spectrometry. Incorporation of [35S]methionine or 32Pi was also studied. For selected proteins, transcript abundance was examined by reverse transcriptase-polymerase chain reaction. Of the 38 protein spots in the region, 23 were identified. Two families showed changes in 2DGE migration or abundance with H2O2 treatment: the peroxiredoxins and two small heat shock protein (Hsp) family members: heat shock 27 kDa protein 1 (Hsp25) and alphaB-crystallin. Peroxiredoxins shifted to lower pI values and this was probably attributable to 'over-oxidation' of active site Cys-residues. Hsp25 also shifted to lower pI values but this was attributable to phosphorylation. alphaB-crystallin migration was unchanged but its abundance decreased. Transcripts encoding peroxiredoxins 2 and 5 increased significantly. In addition, 10 further proteins were identified. For two (glutathione S-transferase pi, translationally-controlled tumour protein), we could not find any previous references indicating their occurrence in cardiac myocytes. We conclude that exposure of cardiac myocytes to oxidative stress causes post-translational modification in two protein families involved in cytoprotection. These changes may be potentially useful diagnostically. In the short term, oxidative stress causes few detectable changes in global protein abundance as assessed by silver-staining.

Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection

Prostaglandins are known to be produced by macrophages when challenged with Trypanosoma cruzi, the etiological agent of Chagas` disease. It is not known whether these lipid mediators play a role in oxidative stress in host defenses against this important protozoan parasite. In this study, we demonstrated that inducible cyclooxygenase-mediated prostaglandin production is a key chemical mediator in the control of parasite burden and erythrocyte oxidative stress during T. cruzi infection in C57BL/6 and BALB/c mice, prototype hosts for the study of resistance and susceptibility in murine Chagas` disease. The results suggested the existence of at least two mechanisms of oxidative stress, dependent or independent with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the mouse strain.

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.

Incubation and rearing temperature effects on Hsp70 levels and heat stress response in broilers

Incubation temperature (IT) was changed to evaluate if 6-wk-old birds become more tolerant to heat stress. After 13 d of incubation, 470 eggs were submitted to low (36.8degreesC), normal (37.8degreesC) and high (38.8degreesC) temperatures. At day 7 post-hatching, 144 birds were allocated to three rearing temperatures (48 birds/treatment): control/thermoneutral (35-24degreesC), high (33-30degreesC) or low (27-18degreesC) according to the age of the birds. Hsp70 levels in tissues of birds (1 d and 42 d), stress response (42 d) and performance were evaluated. High IT decreased brain (P < 0.01) and liver (P < 0.01) Hsp70 levels, whereas low IT decreased brain (P < 0.01) but increased heart (P < 0.01) Hsp70 levels in 1-d-old chicks. Birds incubated at a low temperature had higher (P < 0.05) feed intake (1-42d). High rearing temperature decreased feed intake (P<0.01) and liveweight (P<0.01). Colonic temperature was lower in birds incubated at a low temperature (P < 0.05) and higher in birds reared in a high temperature (P < 0.05) before heat stress. Birds reared in low temperature had higher increase in colonic temperature after heat stress (P < 0.05). Tissue Hsp70 levels were differently affected by rearing temperature, which affected broiler performance more than IT. Lower IT seemed to increase the sensitivity of birds to heat stress at market age.

Effects of Silicon and Drought Stress on Tuber Yield and Leaf Biochemical Characteristics in Potato

Silicon has beneficial effects on many crops, mainly under biotic and abiotic stresses. Silicon can affect biochemical, physiological, and photosynthetic processes and, consequently, alleviates drought stress. However, the effects of Si on potato (Solanum tuberosum L.) plants under drought stress are still unknown. The objective of this study was to evaluate the effect of Si supply on some biochemical characteristics and yield of potato tubers, either exposed or not exposed to drought stress. The experiment was conducted in pots containing 50 dm(3) of a Typic Acrortox soil (33% clay, 4% silt, and 63% sand). The treatments consisted of the absence or presence of Si application (0 and 284.4 mg dm(-3)), through soil amelioration with dolomitic lime and Ca and Mg silicate, and in the absence or presence of water deficit (-0.020 MPa and -0.050 MPa soil water potential, respectively), with eight replications. Silicon application and water deficit resulted in the greatest Si concentration in potato leaves. Proline concentrations increased under lower water availability and higher Si availability in the soil, which indicates that Si may be associated with plant osmotic adjustment. Water deficit and Si application decreased total sugars and soluble proteins concentrations in the leaves. Silicon application reduced stalk lodging and increased mean tuber weight and, consequently, tuber yield, especially in the absence of water stress.