Effects of early life adversity on immediate early gene expression: Systematic review and 3-level meta-analysis of rodent studies.
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ABSTRACT:
SUBMITTER: Schuler H
PROVIDER: S-EPMC8757918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Maternal care refers to the behavior performed by the dam to nourish and protect her litter during its early development. Frequent and high-quality performance of such maternal behaviors is critical for the neurodevelopment of the pups. Maternal exposure to stress during early development can impair maternal care and amplify the deleterious effects of poor maternal caregiving and neglect. As such, a thorough understanding of the effects caused by several models of early life stress on maternal care may yield more insights into the relationship between stress and maternal behavior. Methods: A systematic review was performed to identify and address the effects of early life stress on maternal behavior. The search was conducted using three online databases: PUBMED, Embase, and Web of Science. To provide clear evidence of the impact of stress on maternal care, in every study, the stress group was always compared to a control group. Outcomes were categorized into eight different behaviors: (1) licking/grooming; (2) arched-back nursing; (3) blanket-nursing/passive nursing; (4) nest building; (5) contact with pups; (6) harmful/adverse caregiving; (7) no contact; (8) nest exits. Additionally, the methodological quality of the studies was evaluated. Results: A total of 12 different early life stress protocols were identified from the 56 studies included in this systematic review. Our data demonstrate that different stress models can promote specific maternal patterns of behavior. Regarding the maternal separation protocol, we observed an overall increase in nursing and licking/grooming behaviors, which are essential for pup development. An increase in the number of nest exits, which represents a fragmentation of maternal care, was observed in the limited bedding protocol, but the total amount of maternal care appears to remain similar between groups. Conclusions: Each stress protocol has unique characteristics that increase the difficulty of rendering comparisons of maternal behavior. The increase in maternal care observed in the maternal separation protocol may be an attempt to overcompensate for the time off-nest. Fragmented maternal care is a key component of the limited bedding protocol. Moreover, the methodological approaches to evaluate maternal behavior, such as time, duration, and behavior type should be more homogeneous across studies.
| S-EPMC6724664 | biostudies-literature
Project description:Exposure to early life stress (ELS) causes abnormal hippocampal development and functional deficits in rodents and humans, but no meta-analysis has been used yet to quantify the effects of different rodent models of ELS on hippocampal-dependent memory. We searched PubMed and Web of Science for publications that assessed the effects of handling, maternal separation (MS), and limited bedding and nesting (LBN) on performance in the Morris water maze (MWM), novel object recognition (NOR), and contextual fear conditioning (CFC). Forty-five studies met inclusion criteria (n = 451-763 rodents per test) and were used to calculate standardized mean differences (Hedge's g) and to assess heterogeneity, publication bias, and the moderating effects of sex and species (rats vs. mice). We found significantly lower heterogeneity in LBN compared to handling and MS with no consistent effects of sex or species across the three paradigms. LBN and MS caused similar cognitive deficits in tasks that rely heavily on the dorsal hippocampus, such as MWM and NOR, and were significantly different compared to the improved performance seen in rodents exposed to handling. In the CFC task, which relies more on the ventral hippocampus, all three paradigms showed reduced freezing with moderate effect sizes that were not statistically different. These findings demonstrate the utility of using meta-analysis to quantify outcomes in a large number of inconsistent preclinical studies and highlight the need to further investigate the possibility that handling causes different alterations in the dorsal hippocampus but similar outcomes in the ventral hippocampus when compared to MS and LBN.
| S-EPMC8058062 | biostudies-literature
Project description:Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.
| S-EPMC5608639 | biostudies-literature
Project description:We performed this meta-analysis to elucidate the associations between early-life BPA exposure and reproductive-related outcome indicators. The standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were measured by fixed-effects or random-effects models. The results revealed that BPA exposure at extremely-high dose (>50mg/kg/day) was significantly associated with negative reproductive-related outcomes (Prostate weight: SMD: -4.21; 95% Cl: -5.97, -2.44; Testis weight: SMD: -1.92; 95% Cl: -2.61, -1.23; Epididymis weight: SMD: -2.16; 95% Cl: -3.47, -0.86; Daily sperm production; SMD: -1.90; 95% Cl: -3.27, -0.53; Epididymal sperm count; SMD: -3.42; 95% Cl: -3.87, -2.97). Meanwhile, regardless of the dose, early-life BPA exposure could result in an adverse effect on sperm parameters of F1 generation male rodents at any period. Also, we found the non-monotonic dose response curves of BPA in specific tissues or organs, which may challenge the traditional mindset of "safe dose". This study demonstrated that bisphenol A exposure was relevant to adverse reproductive-related outcomes at specially appointed dose and period of life. Yet the assumption that no adverse effects can occur below the "safe" dose is suspected.
| S-EPMC7585097 | biostudies-literature
Project description:Early-life adversity has been associated with a life-long increased risk for psychopathology and chronic health problems. These long-term negative effects have been explained through stress sensitization, which may involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis through either increased or decreased reactivity. The present meta-analysis assessed for the first time the effect of early-life adversity on cortisol response to social stress. Thirty data sets were included in the meta-analysis, in which early-life adversity and salivary cortisol response to social stress were assessed in 4292 individuals of different ages. Results indicated a moderate effect size (g?=?-0.39) in overall cortisol levels across studies. Separate analyses of cortisol at different stages of response showed large effect sizes at peak and recovery, and a moderate effect at baseline. Heterogeneity was large in this sample of studies and several moderators were identified. The effect size was larger in studies that focused on maltreatment compared to those that included other adversities, and in adults compared to children and adolescents. Percent of women in each sample and methodological quality were positive predictors of the effect size. Publication bias may be present, but the analysis was hampered by the high heterogeneity. Therefore, these results support the association between early-life adversity and blunted cortisol response to social stress, and they suggest that the long-term negative effects of early-life adversity may reach maximum levels in adults.
| S-EPMC5802499 | biostudies-literature
Project description:AimEarly life adversity leads to enduring effects on physical and mental health, school performance and other outcomes. We sought to identify potentially modifiable factors associated with socioeconomic adversity in early life.MethodsWe enrolled 1503 pregnant women aged 16-40 years, without pregnancy complications or pre-existing conditions from Shelby County, Tennessee. Social, familial and economic variables were analysed using principal components (PCs) analyses to generate the Socioeconomic Adversity Index (SAI). This was replicated using the National Survey of Children's Health (NSCH). Health and social outcomes were compared across the quintile groups defined by SAI values at the county, state and national levels.ResultsSignificant differences occurred across the SAI Quintile-1 to Quintile-5 groups in marital status, household structure, annual income, education and health insurance. Significantly worse health and social outcomes occurred in the lower versus higher SAI quintiles, including maternal depression, parental incarceration, child's birthweight and potential for child abuse. Maternal age and race also differed significantly across the SAI quintiles.ConclusionModifiable factors contributing to socioeconomic adversity in early life included marital status, household structure, annual income, education and health insurance. Those exposed to greater socioeconomic adversity as defined by SAI values had significantly worse maternal and child outcomes.
| S-EPMC6584079 | biostudies-literature
Project description:There is a cross-sectional evidence that physical and social environments are linked to childhood adiposity. Evidence is scarce for the role of preconception, pregnancy, and early-life area-level characteristics in shaping childhood adiposity. We aimed to systematically review evidence for associations between physical and social environmental conditions experienced in these periods and childhood adiposity. Published literature was identified from the CINAHL, Embase, MEDLINE, and PsycINFO databases. Longitudinal studies linking an area-level environmental exposure in the preconception, pregnancy, or early-life (less than 1 year) periods and a measure of adiposity between the ages of 2 and 12 years were examined. Eight studies in the United States, Denmark, South Korea, United Kingdom, and Canada satisfied the inclusion criteria. Storm-induced maternal stress, nitrogen oxides exposure, traffic noise, and proximity were associated with greater childhood adiposity. Frequent neighbourhood disturbances were associated with lower adiposity, while particulate matter exposure was associated with both higher and lower adiposity in childhood. Area-level characteristics may play a role in the ongoing obesity epidemic. There is a limited evidence of longitudinal associations between preconception, pregnancy, and early-life area-level characteristics with childhood adiposity. Numerous factors that appear important in cross-sectional research have yet to be assessed longitudinally, both individually and in combination.
| S-EPMC6612509 | biostudies-literature
Project description:Early-life adversity (ELA) is associated with lifelong memory deficits, yet the responsible mechanisms remain unclear. We imposed ELA by rearing rat pups in simulated poverty, assessed hippocampal memory, and probed changes in gene expression, their transcriptional regulation and the consequent changes in hippocampal neuronal structure. ELA rats had poor hippocampal memory and stunted hippocampal pyramidal neurons, associated with ~140 differentially expressed genes. Upstream regulators of the altered genes included glucocorticoid receptor and, unexpectedly, the transcription factor neuron-restrictive silencer factor (NRSF/REST). NRSF contributed critically to the memory deficits because blocking its function transiently following ELA rescued spatial memory and restored the dendritic arborization of hippocampal pyramidal neurons in ELA rats. Blocking NRSF function in vitro augmented dendritic complexity of developing hippocampal neurons, suggesting that NRSF represses genes involved in neuronal maturation. These findings establish important, surprising contributions of NRSF to ELA-induced transcriptional programming that disrupts hippocampal maturation and memory function.
2020-12-15 | GSE161498 | GEO
Project description:Vitamin D deficiency has been linked to an increased risk of asthma. This study aimed to quantify the effect of early life vitamin D status on asthma and wheeze later in life.PubMed, Embase, CINAHL, and CNKI databases, the Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 2017. We included randomized controlled trials (RCTs) and cohort studies with vitamin D level in blood (maternal or cord or infant) or intake (maternal intake during pregnancy or infant intake) and asthma and/or wheeze. Two reviewers independently extracted data. Fixed- and random-effects models were used to summarize the risk estimates of comparisons between highest vs. lowest vitamin D categories.Of the 1485 studies identified, three RCTs and 33 cohort studies were included. We did not include the RCTs (1619 participants) in the meta-analysis as the comparators and outcome definitions were heterogenous. Three RCTs reported a non-statistically significant effect of vitamin D supplementation during pregnancy on offspring wheeze/asthma at 3 years of age. Pooled estimates of cohort studies suggest no association between antenatal blood vitamin D levels or vitamin D intake and offspring asthma assessed either >?5 years or???5 years. The estimate for blood vitamin D remained unchanged when two studies assessing asthma in adulthood were excluded, but a significant inverse association emerged between vitamin D intake and childhood asthma. We found no association between antenatal vitamin D level and wheeze. On the other hand, vitamin D intake during pregnancy may have a protective effect against wheeze.The pooled estimates from cohort studies show no association between antenatal blood vitamin D level and asthma/wheeze in later life. Whereas, the pooled estimates from cohort studies suggest that antenatal vitamin D intake may have an effect on childhood asthma >?5 years or childhood wheeze. The inconsistent results from studies assessing vitamin D either in blood or intake may be explained by previously reported non-linear association between blood vitamin D3 and childhood asthma. Further trials with enough power and longer follow-up time should be conducted to confirm the results.
| S-EPMC6053833 | biostudies-other
Project description:Background: The relationship between adiposity at birth and in childhood, and telomere length is yet to be determined. We aimed to systematically review and meta-analyse the results of studies assessing associations between neonatal and later childhood adiposity, and telomere length. Methods: We searched Medline, EMBASE and PubMed for studies reporting associations between adiposity measured in the neonatal period or later childhood/adolescence, and leucocyte telomere length, measured at any age via quantitative polymerase chain reaction, or terminal restriction fragment analysis, either cross-sectionally, or longitudinally. Papers published before April 2017 were included. Results: Out of 230 abstracts assessed, 23 papers (32 estimates) were retained, from which 19 estimates were meta-analysed (15 cross-sectional, four longitudinal). Of the 15 cross-sectional estimates, seven reported on neonates: four used binary exposures of small-for-gestational-age vs. appropriate-for-gestational age (or appropriate- and large-for-gestational age), and three studied birth weight continuously. Eight estimates reported on later childhood or adolescent measures; five estimates were from studies of binary exposures (overweight/obese vs. non-obese children), and three studies used continuous measures of body mass index. All four longitudinal estimates were of neonatal adiposity, with two estimates for small-for-gestational-age vs. appropriate-for-gestational age neonates, and two estimates of birth weight studied continuously, in relation to adult telomere (49-61 years). There was no strong evidence of an association between neonatal or later childhood/adolescent adiposity, and telomere length. However, between study heterogeneity was high, and there were few combinable studies. Conclusions: Our systematic review and meta-analysis found no strong evidence of an association between neonatal or later childhood or adolescent adiposity and telomere length.
| S-EPMC6259597 | biostudies-literature