Clinical and preclinical research both indicate that early life adversities alter sensitivity to stress well into adulthood. Although clinical research identifies infancy, childhood, and adolescence as periods of heightened vulnerability, the majority of preclinical research experiments have examined the enduring impact of stressors delivered either prenatally or prior to weaning. It was recently shown that exposing rats to intermittent stressors across the childhood/ adolescent period (PD 21-51) increased their behavioural and endocrine sensitivity to stress in adulthood. The purpose of the current project was to determine whether specific developmental periods are differentially sensitive to the lasting effects of intermittent stress. Male and female Long-Evans rats were exposed to three stressors (foot shock, elevated platform exposure, and cold water emersion) two times each, randomly over a twelve day period (childhood: PD 22-33 vs. adolescence: PD 35-46). Age-matched controls were briefly handled on each of the stressor application days. After completion of the stress exposure period, rats were left undisturbed for 27 days and behavioural testing commenced in adulthood. Intermittent physical stress exposure during the childhood period increased anxiety-like behaviours in adulthood, as indexed by the Elevated-Plus Maze (EPM) and Shock Probe Burying Test (SPBT). This also increased depression-like behaviour in adult male rats and decreased depression-like behaviour in adult female rats, as indexed by the Forced Swim Test (FST). Intermittent physical stress exposure in the adolescent period increased open-arm activity, increased burying behaviour and increased immobility in the forced swim test, in both male and female rats. Stress during either developmental period, failed to alter corticosterone (CORT) reactivity to restraint stress in adulthood. Thus, it appears that the long lasting behavioural impact of early-life adversity can vary, according to the developmental period the stressors are experienced in, but this is further modified by sex and the type of test used to evaluate adult behaviour. / Thesis (Master, Psychology) -- Queen's University, 2010-08-25 18:53:24.136

There is a paucity of research examining the neurobiological functioning of new mothers who have experienced parental loss during development. The current study investigated the relationship between inconsistent (IC) versus consistent (CC) care and brain activity in regions that comprise a putative neurobiological model of mothering. Mothers were shown positive and negative pictures of their own and an unfamiliar infant. Through repeated measures ANOVAs, it was found that BOLD activity was greater for own infant in the nucleus accumbens (NAC) and amygdala (AMY) and that positive pictures elicited greater BOLD response in the NAC, AMY and anterior cingulate cortex. Interestingly, IC mothers show an even greater response own infant in the NAC and left hypothalamus (HYPO). In the left dorsolateral prefrontal cortex, IC mothers showed greater BOLD response to other infant. Thus, functioning of the maternal circuit, which includes areas strongly implicated in reward, may be altered by early experiences.

There is a paucity of research examining the neurobiological functioning of new mothers who have experienced parental loss during development. The current study investigated the relationship between inconsistent (IC) versus consistent (CC) care and brain activity in regions that comprise a putative neurobiological model of mothering. Mothers were shown positive and negative pictures of their own and an unfamiliar infant. Through repeated measures ANOVAs, it was found that BOLD activity was greater for own infant in the nucleus accumbens (NAC) and amygdala (AMY) and that positive pictures elicited greater BOLD response in the NAC, AMY and anterior cingulate cortex. Interestingly, IC mothers show an even greater response own infant in the NAC and left hypothalamus (HYPO). In the left dorsolateral prefrontal cortex, IC mothers showed greater BOLD response to other infant. Thus, functioning of the maternal circuit, which includes areas strongly implicated in reward, may be altered by early experiences.

This study examined the demography of giant kelp Macrocystis pyrifera (Linnaeus) and its interactions with understorey algae and invertebrates in southern New Zealand over two and a half years. Most of the study was done at two sites within Akaroa Harbour (Banks Peninsula) but ancillary sites at Tory Channel (Marlborough Sounds) were used for parts of the study. The kelp forests within Akaroa Harbour were generally highly productive, with a high annual turnover of giant kelp. Macrocystis plants were mostly annual and rarely reached ages greater than 12 months. Peak recruitment occurred in spring (November) during 1995-97, but lesser recruitment episodes occurred throughout the year. The maximum growth rates of Macrocystis fronds were comparable to rates reported elsewhere in southern hemisphere populations (22 mm - 24.5 mmlday), but considerably lower than those in northern hemisphere populations. The major experiment incorporated in the study tested the effects of the Macrocystis canopy and the understorey canopy of the stipitate laminarian Ecklonia radiata on macroalgae and invertebrates. The experiment was structured so that the effects of clearances at different times could be determined. One impetus for this experiment was the need to address issues relating to the commercial harvesting of giant kelp, its sustainability and its effects on other species. The effects of canopy removals on understorey algae, mostly juvenile Macrocystis, Ecklonia and Carpophyllum spp, were highly dependent on the timing of canopy removals and the combinations of canopies removed. For example, winter harvests of the Macrocystis canopy alone enhanced the survival of post-settlement Macrocystis recruits, but had little effect on Ecklonia recruitment. However, when both Macrocystis and Ecklonia canopies were removed in spring, there was heavy recruitment of Ecklonia that grew to dominate the understorey. Strong inter and intraspecific interactions from the Macrocystis surface canopy appeared to have been reduced by physical factors including water turbidity, sedimentation and the deterioration of the surface canopy during summer. These physical factors were not as limiting in Tory Channel. Fine scale extrinsic factor effects including nutrients, light and grazing on the early life history of Macrocystis were investigated in small experiments. Results suggest that recruitment may be nutrient limited even at moderately low temperatures, and that small herbivorous gastropods are an important source of mortality in the early life stages of Macrocystis. Culturing and transplantation cultivation techniques were also examined as a means of supplementing algal supplies. Macrocystis was cultured successfully through its life cycle onto culture ropes, but generally failed to produce visible sporophytes when placed in the field. Cultured plants did grow in Tory Channel, however. Juvenile plants transplanted to ropes for on-farm cultivation showed little growth during summer, but the addition of nutrients significantly enhanced growth rates of these plants during warmer months when natural nutrient levels were low. Increased growth rates at the onset of winter and with the addition of nutrients during summer confirmed that low nutrient levels during summer are growth limiting. Akaroa Harbour kelp forests exhibited considerable variation in Macrocystis canopy biomass through time. For example, the 32,000 m2 kelp forest at Wainui had a biomass of 144 t in October 1995, which then decreased to 21 t in October 1996. Canopies tended to deteriorate during summer. Thus, at Ohinepaka Bay kelp forest had a biomass of 31 t during winter 1997, which decreased to 0.06 t the following summer. The greatest reduction in biomass, however, coincided with a period of hugely increased sediment, which smothered blades in the sea-surface canopy, covered the substratum, and prevented successful recruitment of kelp for over a year. Nutrient depletion was one of several factors thought to cause the summer deterioration of the Macrocystis sea-surface canopy, which has important ramifications for the commercial harvesting of Macrocystis pyrifera in summer. Management considerations and options are discussed in relation the commercial harvesting of Macrocystis in New Zealand. The major conclusion of this study is that although Macrocystis was able to form dense surface canopies during winter its ability to dominate kelp forests was constrained by physical factors, especially sedimentation, high turbidity, nutrients, and storms. The lack of strong interactions between Macrocystis and Ecklonia are also largely a result of their different life history characteristics. Overall, there appear to be no significant negative flow-on effects resulting from kelp harvesting and it appears that Macrocystis can be harvested sustainably.

Scaphirhynchus sturgeons are species of concern throughout their ranges. To revitalize their populations, a thorough understanding of their habitat use during all life stages is critical. However, limited information exists about fine-scale habitat use during early life. To determine the feasibility of using radio telemetry to monitor habitat use in the field, I assessed growth and survival of age-0 sturgeon tagged with 0.2 g, non-functioning telemetry tags during an eight-week period in a controlled setting and then tested field performance in the Middle Mississippi River (MMR). Three treatments were evaluated: 1) control, 2) internally implanted tags, and 3) externally attached tags. Growth and survival varied across treatment groups (all comparisons P<0.05). Sturgeon with internally implanted tags grew slowly and had low survival, while sturgeon within the control group and those with external tags grew faster and had higher survival (~100%). A trial was conducted to determine swimming performance of each of the treatment groups, which resulted in no differences in critical swimming speed among the tag types. Based on these results, a field-based telemetry evaluation was performed to determine if it is feasible to monitor fine-scale habitat use. Four wild, age-0 Scaphirhynchus sturgeon were externally tagged with functioning radio transmitters in the MMR. After less than 24-h, the tagged fish were no longer detectable, likely due to environmental conditions (e.g., extreme depths and high conductivity). Thus, efforts should be directed to creating a small telemetry transmitter that uses technology (e.g., ultrasonic) that transmits well in deep rivers while maintaining a minimum tag weight and maximizing battery life. Fine scale habitat use of age-0 sturgeon may ultimately be able to be quantified in the MMR and other deep rivers in the future, if technologies improve.

Preterm infants are at increased risk of cardiometabolic and neurodevelopmental disorders in later life. The typical postnatal growth pattern of failure to achieve the equivalent of a normal fetal growth rate, followed up by catch-up growth, altered adiposity and altered hypothalamic-pituitary-adrenal axis (HPA) activity may be predisposing factors. Potential mechanisms that may mediate such programmed effects include altered DNA methylation and faster telomere attrition. A prospective cohort of 46 very preterm (25+2 to 31+5 weeks’ gestation, mean 28.6) and 40 full term (38+3 to 42+2 weeks’ gestation, mean 40.2) infants was established to investigate potential mechanisms. Infants were studied at birth, term equivalent age, 3 months and 1 year corrected for prematurity. At all time points, linear growth and body composition (by densitometry) were measured and buccal (epithelial) cells was collected for measurement of DNA methylation (5mC) and relative telomere length. Compared with full term infants, preterm infants were lighter (p < 0.001) and had a smaller head circumference (p < 0.05) at all time-points and were shorter at term equivalent (p < 0.001) and 3 months corrected age (p = 0.002). Preterm infants also had greater percentage body fat at term equivalent age (mean difference = 5.5%, p < 0.001), which normalised by 3 months corrected (mean difference = 0.9%, p = 0.4). Preterm infants had a blunted salivary cortisol response (mean difference 0.4 μg/dL, p = 0.02) to a stressor (physical examination) at 3 months compared to term infants at this age, suggesting altered activity of the HPA axis. 5mC is fundamental in the control of expression of imprinted genes involved in fetal growth. Notably, a number of studies in humans exposed to an adverse environment in early life have demonstrated altered 5mC at the differentially methylated regions (DMRs) controlling the expression of the key fetal growth factor insulin like growth factor 2 (IGF2) and at the linked H19 imprinting control region (H19 ICR). At birth, preterm infants had a significant decrease in 5mC at DMR2 compared with term infants at birth (β = –11.5, p < 0.001) and compared with preterm infants at term equivalent age (mean difference = -7.4, p = 0.01). By term equivalent age, preterm infants had decreased 5mC at both DMR2 (β = –2.8, p = 0.01) and the H19 ICR (β = –2.3, p = 0.048) compared with term infants at birth, although this difference disappeared at 1 year corrected. Although research has suggested that catch up growth may confer an unfavourable metabolic phenotype, poor initial weight gain can associate with worse cognitive outcome. A pathway was established for obtaining advanced magnetic resonance images of the preterm brain. 5mC at H19 ICR and DMR2 in buccal DNA showed no association with measures of white matter microstructure or whole brain volumes. Term infants demonstrated telomere lengthening over the first year of life (mean difference = -0.3, p = 0.02). There was no significant change in telomere length over the first year of life in preterm infants (mean difference = 0.2, p = 0.34). However, as preterm infants at term equivalent age had longer telomeres compared to term infants at birth (β = 0.6, p < 0.001), ultimately there were no differences between the term and the preterm groups at 1 year corrected age (β = 0.3, p = 0.07). The DNA modification 5-hydroxymethylcytosine (5hmC) is a stable modification in its own right and is also thought to be an intermediate step in DNA demethylation. 5hmC is abundant in the placenta but has not been studied in the context of fetal programming. Additionally, previous research using methods such as bisulphite conversion would not have discriminated between 5mC and 5hmC and therefore the role of 5mC may not have been accurately measured. To study the relationship between 5mC, 5hmC and fetal growth, gene expression of candidate imprinted and non-imprinted genes in full term placental samples from the Edinburgh Reproductive Tissue BioBank was analysed. 5mC and 5hmC within the IGF2/H19 and KvDMR (controlling CDKN1C) loci was estimated using chemical capture and immunoprecipitation techniques that discriminate between modifications. Relationships between the expression of IGF2 (r = 0.3, p = 0.02) and CDKN1C (r = -0.3, p = 0.01) and birth weight across the normal range were found and in keeping with the known action of these genes. 5mC at IGF2 DMR0 (β = 0.3, p = 0.02) and KvDMR (β = 0.3, p = 0.02) and 5hmC at H19 gene body (β = 0.2, p = 0.04) associated with birth weight. Thus, DNA modifications at imprinted DMRs may modulate environmental influences on fetal growth across the normal range. DNA methylation at IGF2/H19 can be influenced by early life events. It remains to be seen whether any changes are present later in childhood and whether they associate with risk factors for the metabolic syndrome.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18337号 / 農博第2062号 / 新制||農||1023(附属図書館) / 学位論文||H26||N4844(農学部図書室) / 31195 / 京都大学大学院農学研究科応用生物科学専攻 / (主査)教授 荒井 修亮, 教授 山下 洋, 准教授 田川 正朋 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Early life stress is a prevalent problem affecting many worldwide and can be experienced in a variety of ways, including limited access to resources as in many low socioeconomic status households. In humans, exposure to stress early in life is linked to various psychiatric conditions such as substance use disorder, attention-deficit/hyperactivity disorder, and gambling. One characteristic that these disorders share is elevated impulsivity. Impulsivity is a multifaceted construct and often behaviors are classified as either an impulsive choice (e.g., inability to delay gratification) or an impulsive action (e.g., inability to inhibit premature responses). In the first set of experiments presented here, we characterize the limited bedding and nesting model (LBN) of early life adversity in rodents, in which rat dams and their pups are housed in a limited resource environment from postnatal day (PND) 2 through 9. This model works by inducing stress in the dams, which alters their maternal care behaviors towards pups. As a result, this altered care can be stressful for the developing pups. We have found that LBN exposure promoted resilience to addiction-related phenotypes in adult male, but not female rats. Specifically, LBN reduced impulsive choice, morphine self-administration, and nucleus accumbens (NAc) glutamate transmission in males, effects not seen in females. Additionally, changes in NAc gene transcription unique to LBN males may contribute to resilience. We build on these findings in the second set of experiments, which explores whether LBN alters impulsive action, risky decision-making, and the gene transcriptome of the orbitofrontal cortex (OFC). We found that LBN increased impulsive action in males. Additionally, we found LBN exposure in rats across sex reduces risky choice. These changes in behavior were accompanied by highly specific changes in gene transcription in the OFC, which is a brain region that mediates both impulsive and risky decision-making behaviors. The identification of genes and signaling pathways that are altered by LBN in the male OFC lays the groundwork for future studies investigating the mechanisms by which early life stress alters addiction-related phenotypes. / Psychology

Pharmaceuticals have routinely been detected in the environment resulting in a growing concern about whether these drugs could elicit effects on aquatic organisms. The concerns are centered on the highly conserved nature of mammalian therapeutic targets in fish. These pharmaceuticals are found at very low levels in the environment, which can result in sub-lethal effects in aquatic organisms. Therefore, 28 d early-life stage studies were conducted on six pharmaceuticals to assess their impacts on survival and growth fathead minnow larvae. Two pharmaceuticals tested, carbamazepine and fenofibrate, resulted in no alterations to survival and growth. However, amiodarone, clozapine, dexamethasone, and levonorgestrel (LNG) reduced survival at concentrations tested with LNG being the most potent at 462 ng/L. Survival was increased with amiodarone and clozapine; however LNG significantly decreased growth at 86 ng/L. Therefore, the most potent pharmaceutical tested was the synthetic progestin LNG with survival and growth impacts at concentrations less than 1 μg/L. Further analysis was conducted by measuring specific endocrine related mRNA transcript profiles in FHM larvae following the 28 d ELS exposure to LNG. Transcripts of 3β-HSD, 20β-HSD, and FSH were significantly down-regulated following 28 d exposure to both 16.3 and 86.9 ng/L LNG. Also, CYP19a expression was significantly down-regulated at 86.9 and 2392 ng/L LNG. Subsequently, a second study examined time periods that may be most sensitive (e.g., windows of sensitivity) for FHM larvae exposed to LNG. Larvae were exposed to a single concentration of LNG (i.e. LOECgrowth of 86.2 ng/L as determined in the 28 d ELS study) for different time periods starting with fertilized egg through 28 dph. Growth and mRNA expression of the four differentially expressed transcripts from the first study were measured. Regardless of the duration of exposure, LNG significantly decreased growth in fathead minnow larvae at day 28. For both 20β-HSD and CYP19a, mRNA expression was decreased following exposure to LNG; however, these transcripts returned to baseline levels after removal of LNG. 3β-HSD and FSH showed similar trends after exposure to LNG with 7-14 d and 14-28 d exposures exhibiting a decrease in expression; however, FSH expression returned to baseline once removed for LNG exposure. Based on these data, 3β-HSD was the only transcript to remain down regulated after LNG exposure. Together these data suggest LNG can negatively impact FHM larval survival and growth, with significant alterations in endocrine related responses. However, these changes in endocrine related responses may not directly correlate to the changes in growth demonstrated with LNG exposure to fathead minnows. Therefore, additional research is warranted to ascertain additional mechanisms, either endocrine related or non-endocrine functions, related to changes in growth of larval fathead minnows.

No description available.