scholarly journals The long-term consequences of early-life dexamethasone treatment on the cognitive ability of male mice and gene expression in the hippocampus

2018 ◽  
pp. 8-8
Keyword(s):  
Gene Expression ◽  
Cognitive Ability ◽  
Early Life ◽  
Male Mice ◽  
Dexamethasone Treatment ◽  
Long Term Consequences

scholarly journals Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience

2015 ◽  
Vol 53 ◽  
pp. 69-81 ◽  
Author(s):  
Benjamin D. Sachs ◽  
Ramona M. Rodriguiz ◽  
Ha L. Tran ◽  
Akshita Iyer ◽  
William C. Wetsel ◽  
...  
Keyword(s):  
Early Life ◽  
Life Experience ◽  
Early Life Experience ◽  
Serotonin Deficiency ◽  
Long Term Consequences

scholarly journals Early-life circumstances and the risk of function-limiting long-term conditions in later life

2020 ◽  
Vol 11 (2) ◽  
pp. 157-180
Author(s):  
Matthew H. Iveson ◽  
Chris Dibben ◽  
Ian J. Deary
Keyword(s):  
Life Course ◽  
Cognitive Ability ◽  
Early Life ◽  
Economic Status ◽  
Functional Limitation ◽  
Later Life ◽  
Socio Economic Status ◽  
Childhood Cognitive Ability ◽  
The Life Course

Older adults are particularly prone to function-limiting health issues that adversely affect their well-being. Previous work has identified factors from across the life course –childhood socio-economic status, childhood cognitive ability and education – that predict later-life functional outcomes. However, the independence of these contributions is unclear as later-in-the-life-course predictors are themselves affected by earlier ones. The present study capitalised on the recent linkage of the Scottish Mental Survey 1947 with the Scottish Longitudinal Study, using path analyses to examine the direct and indirect associations between life-course predictors and the risk of functional limitation at ages 55 (N = 2,374), 65 (N = 1,971) and 75 (N = 1,534). The odds of reporting a function-limiting long-term condition increased across later life. At age 55, reporting a functional limitation was significantly less likely in those with higher childhood socio-economic status, higher childhood cognitive ability and higher educational attainment; these associations were only partly mediated by other predictors. At age 65, adult socio-economic status emerged as a mediator of several associations, although direct associations with childhood socio-economic status and childhood cognitive ability were still observed. At age 75, only childhood socio-economic status and adult socio-economic status directly predicted the risk of a functional limitation, particularly those associated with disease or illness. A consistent pattern and direction of associations was observed with self-rated health more generally. These results demonstrate that early-life and adult circumstances are associated with functional limitations later in life, but that these associations are partly a product of complex mediation between life-course factors.

scholarly journals SUN-207 Modelling Long Term Glucocorticoid-Induced HPA Axis Suppression in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nicola Romano ◽  
Peter James Duncan ◽  
Oscar Nolan ◽  
Paul Roussel Le Tissier ◽  
Mike Shipston ◽  
...  
Keyword(s):  
Drinking Water ◽  
Mouse Model ◽  
Hpa Axis ◽  
Adult Male ◽  
Male Mice ◽  
Dexamethasone Treatment ◽  
Mortality And Morbidity ◽  
Fold Reduction ◽  
The Uk

Abstract Glucocorticoids are prescribed for >3 months to 1% of the UK population. 10-50% of these long-term glucocorticoid treated patients develop persistent HPA axis suppression associated with mortality and morbidity. We have developed a mouse model of glucocorticoid-induced HPA axis dysfunction to determine the mechanisms resulting in persistent HPA axis suppression. Experiment 1: 36 C57BL/6 adult male mice received Dexamethasone (DEX,~10µg/day) or vehicle (CTL) via drinking water for 28 days, following which treatment was stopped and tissues were harvested at 0, 7 and 28 days. DEX suppressed waking serum corticosterone at days 0 and 7, recovering by day 28. Adrenal size remained lower 28 days following DEX withdrawal. DEX had no effect on whole pituitary pomc, nr3c1 or crhr1 expression, although avpr1b was increased at day 0. In the adrenal, hsd3b2 and cyp11a1 expression were reduced at time 0; normalising by 28 days. Experiment 2: 24 POMC-GFP male mice were treated as above. Tissues were collected at day 0 (n=6), 7 (n=3) and 10 (n=3) following withdrawal. Pooled corticotrophs (groups of 3) were isolated by FACS and RNA extracted for qPCR. DEX reduced corticotroph pomc expression at time 0 (x20 fold reduction), with x5 fold suppression at day 7, which recovered with evidence of compensation by day 10. DEX increased expression of avpr1b but not crhr1. CONCLUSION: 28 days dexamethasone treatment in mice suppresses the HPA axis. HPA suppression is evident 7 days following withdrawal of dexamethasone in the adrenal, corticotroph population and corticosterone production. Further analysis will determine mechanisms for delays in HPA axis recovery.

scholarly journals Developmental conditions modulate DNA methylation at the glucocorticoid receptor gene with cascading effects on expression and corticosterone levels in zebra finches

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Blanca Jimeno ◽  
Michaela Hau ◽  
Elena Gómez-Díaz ◽  
Simon Verhulst
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Glucocorticoid Receptor ◽  
Early Life ◽  
Receptor Gene ◽  
Regulatory Region ◽  
Long Term Effects ◽  
Glucocorticoid Receptor Gene ◽  
Developmental Conditions

Abstract Developmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor gene Nr3c1 has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of the Nr3c1 gene in blood. Having been reared in a large brood induced higher DNA methylation of the Nr3c1 regulatory region in adulthood, and this effect persisted over years. Nr3c1 expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect on Nr3c1 methylation at our target region. Nr3c1 expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of the Nr3c1 regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.

scholarly journals From egg to embryo: a peripatetic journey

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 825-828 ◽  
Author(s):  
Richard M Schultz
Keyword(s):  
Gene Expression ◽  
Assisted Reproductive Technologies ◽  
Egg Quality ◽  
Reproductive Technologies ◽  
Molecular Signature ◽  
High Quality ◽  
Long Term Consequences ◽  
The Uk ◽  
Effect Gene

The recent surge of interest in oocyte development has been spurred in large part by the increasing implementation of assisted reproductive technologies (ART) to treat human infertility. What is becoming apparent is that ‘egg quality’ is a primary factor in the success of ART (Sauer 1998), and yet we know virtually nothing about the molecular signature of a ‘high quality’ oocyte, i.e., an oocyte that is capable of maturing, being fertilized and supporting development to term. We are gaining marked insights, however, into how sperm activate eggs and the changes in gene expression that accompany preimplantation development. Nevertheless, embryo culture is known to effect gene expression (Rinaudo & Schultz 2004), the long-term consequences of which are only recently being unmasked. This review will briefly highlight these topics that were presented during the Biennial Joint Meeting of the UK Fertility Societies at Warwick University in April 2005.

scholarly journals Early-Life Exposure to Low-Dose Cadmium Accelerates Diethylnitrosamine and Diet-Induced Liver Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hongbo Men ◽  
Jamie L. Young ◽  
Wenqian Zhou ◽  
Haina Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Early Life ◽  
Low Dose ◽  
Liver Tumors ◽  
Cadmium Exposure ◽  
Male Mice ◽  
Nonalcoholic Fatty Liver ◽  
Early Life Exposure ◽  
The Impact

Maternal exposure to cadmium causes obesity and metabolic changes in the offspring, including nonalcoholic fatty liver disease-like pathology. However, whether maternal cadmium exposure accelerates liver cancer in the offspring is unknown. This study investigated the impact of early-life exposure to cadmium on the incidence and potential mechanisms of hepatocellular carcinoma (HCC) in offspring subjected to postweaning HCC induction. HCC in C57BL/6J mice was induced by diethylnitrosamine (DEN) injection at weaning, followed by a long-term high-fat choline-deficient (HFCD) diet. Before weaning, liver cadmium levels were significantly higher in mice with early-life cadmium exposure than in those without cadmium exposure. However, by 26 and 29 weeks of age, hepatic cadmium fell to control levels, while a significant decrease was observed in copper and iron in the liver. Both male and female cadmium-exposed mice showed increased body weight compared to non-cadmium-treated mice. For females, early-life cadmium exposure also worsened insulin intolerance but did not significantly promote DEN/HFCD diet-induced liver tumors. In contrast, in male mice, early-life cadmium exposure enhanced liver cancer induction by DEN/HFCD with high incidence and larger liver tumors. The liver peritumor tissue of early-life cadmium-exposed mice exhibited greater inflammation and disruption of fatty acid metabolism, accompanied by higher malondialdehyde and lower esterified triglyceride levels compared to mice without cadmium exposure. These findings suggest that early-life exposure to low-dose cadmium accelerates liver cancer development induced by a DEN/HFCD in male mice, probably due to chronic lipotoxicity and inflammation caused by increased uptake but decreased consumption of fatty acids.

A long-term study of the effects of housing conditions on the welfare of domestic pigs

1993 ◽  
Vol 1993 ◽  
pp. 86-86
Author(s):  
M. Mendl ◽  
D.M. Broom ◽  
A.J. Zanella
Keyword(s):  
Early Life ◽  
Group Housing ◽  
Housing Conditions ◽  
Term Study ◽  
Housing Systems ◽  
Long Term Study ◽  
Alternative Systems ◽  
Long Term Consequences ◽  
Over Time

In view of the forthcoming UK ban on stall and tether housing for sows, the long-term consequences of housing pregnant pigs in alternative systems were assessed. The objective of the study was to examine the effects of two indoor group-housing systems on measures of the welfare of pregnant pigs, and to compare pigs housed in these systems with pigs housed in stalls. The study followed 63 female pigs from early life until their fourth pregnancy. A longitudinal experimental design was used to obtain information on how the pigs responded to their initial introduction to the three housing systems (during the first pregnancy), and how they adjusted to the systems over time (in the fourth pregnancy).

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