Early life opioid exposure and potential long-term effects.
Ontology highlight
ABSTRACT:
SUBMITTER: Harder HJ
PROVIDER: S-EPMC6629922 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:While adult exposure to PCE is known to have toxic effects, there is little information on the long-term impact of prenatal and early childhood exposure. We undertook a retrospective cohort study to examine the effects of their early life exposure to PCE-contaminated drinking water. This retrospective cohort study examined whether prenatal and early childhood exposure to PCE-contaminated drinking water influenced the risk of a variety of chronic conditions among adults who were born between 1969 and 1983 in the Cape Cod area of Massachusetts.Eight hundred and thirty-one participants with prenatal and early childhood PCE exposure and 547 unexposed participants were studied. Individuals completed questionnaires to gather information on demographic characteristics, chronic conditions, and other sources of solvent exposure. The location of residences from birth through 1990 were used to estimate PCE exposure with U.S. EPA's water distribution system modeling software (EPANET) modified to incorporate a leaching and transport model.No associations were observed between early life PCE exposure and current occurrence of obesity, diabetes, cardiovascular disease, hypertension, color blindness, near- and far sightedness and dry eyes. In contrast, a 1.8-fold increased risk of cancer (95% CI: 0.8, 4.0) was seen among individuals with any early life exposure. These results were based on 31 participants (23 exposed and 8 unexposed) who reported cancers at a variety of anatomical sites, particularly the cervix. A 1.5-fold increase in the risk of epilepsy (95% CI: 0.6, 3.6, based on 16 exposed and 7 unexposed participants) was also observed among individuals with any early life exposure that was further increased to 1.8 (95% CI: 0.7, 4.6) among those with exposure at or above the sample median.These results suggest that the risk of epilepsy and certain types of cancer such as cervical cancer may be increased among adults who were exposed to PCE-contaminated drinking water exposure during gestation and early childhood. These findings should be interpreted cautiously because of the study limitations and confirmed in follow-up investigations of similarly exposed populations with medically-confirmed diagnoses. This relatively young study population should also be monitored periodically for subsequent changes in disease risk.
| S-EPMC4397674 | biostudies-other
Project description:Ivermectin is a broad-spectrum antiparasitic medicine, which is often used as a treatment for parasites or as a prophylaxis. While studies have looked at the long-term effects of Ivermectin on helminths, studies have not considered the long-term impacts of this treatment on host health or disease susceptibility. Here, we tracked the effects of early life Ivermectin treatment in Cuban tree frogs (Osteopilus septentrionalis) on growth rates, mortality, metabolically expensive organ size, and susceptibility to Batrachochytrium dendrobatidis (Bd) infection. One year after exposure, there was no effect of Ivermectin exposure on frog mass (X21 = 0.904, p = 0.34), but when tracked through the exponential growth phase (~2.5 years) the Ivermectin exposed individuals had lower growth rates and were ultimately smaller (X21 = 7.78, p = 0.005; X21 = 5.36, p = 0.02, respectively). These results indicate that early life exposure is likely to have unintended impacts on organismal growth and potentially reproductive fitness. Additionally, we exposed frogs to Bd, a pathogenic fungus that has decimated amphibian populations globally, and found early life exposure to Ivermectin decreased disease susceptibility (disease load: X21 = 17.57, p = 0.0002) and prevalence (control: 55%; Ivermectin: 22%) over 2 years after exposure. More research is needed to understand the underlying mechanism behind this phenomenon. Given that Ivermectin exposure altered disease susceptibility, proper controls should be implemented when utilizing this drug as an antiparasitic treatment in research studies.
| S-EPMC8513825 | biostudies-literature
Project description:BackgroundThere is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications.ObjectivesOur goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models.MethodsWe examined the current literature and identified relevant studies through PubMed by using combinations of the search terms "arsenic", "in utero", "transplacental", "prenatal" and "fetal".DiscussionEcological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects.ConclusionsAs millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels.
| S-EPMC3783578 | biostudies-literature
Project description:Warming and hypoxia are two stressors commonly found within natural salmon redds that are likely to co-occur. Warming and hypoxia can interact physiologically, but their combined effects during fish development remain poorly studied, particularly stage-specific effects and potential carry-over effects. To test the impacts of warm water temperature and hypoxia as individual and combined developmental stressors, late fall-run Chinook salmon embryos were reared in 10 treatments from fertilization through hatching with two temperatures [10°C (ambient) and 14°C (warm)], two dissolved oxygen saturation levels [normoxia (100% air saturation, 10.4-11.4 mg O2/l) and hypoxia (50% saturation, 5.5 mg O2/l)] and three exposure times (early [eyed stage], late [silver-eyed stage] and chronic [fertilization through hatching]). After hatching, all treatments were transferred to control conditions (10°C and 100% air saturation) through the fry stage. To study stage-specific effects of stressor exposure we measured routine metabolic rate (RMR) at two embryonic stages, hatching success and growth. To evaluate carry-over effects, where conditions during one life stage influence performance in a later stage, RMR of all treatments was measured in control conditions at two post-hatch stages and acute stress tolerance was measured at the fry stage. We found evidence of stage-specific effects of both stressors during exposure and carry-over effects on physiological performance. Both individual stressors affected RMR, growth and developmental rate while multiple stressors late in development reduced hatching success. RMR post-hatch showed persistent effects of embryonic stressor exposure that may underlie differences observed in developmental timing and acute stress tolerance. The responses to stressors that varied by stage during development suggest that stage-specific management efforts could support salmon embryo survival. The persistent carry-over effects also indicate that considering sub-lethal effects of developmental stressor exposure may be important to understanding how climate change influences the performance of salmon across life stages.
| S-EPMC8271147 | biostudies-literature
Project description:BackgroundArsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood.ObjectiveWe aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice.MethodsC57BL/6 mice were exposed to arsenic in utero and throughout postnatal life. At 1 week of age, a subgroup of mice were infected with influenza A. We then assessed the acute and long-term effects of arsenic exposure on viral clearance, inflammation, lung structure, and lung function.ResultsEarly life arsenic exposure reduced the clearance of and exacerbated the inflammatory response to influenza A, and resulted in acute and long-term changes in lung mechanics and airway structure.ConclusionsIncreased susceptibility to respiratory infections combined with exaggerated inflammatory responses throughout early life may contribute to the development of bronchiectasis in arsenic-exposed populations.
| S-EPMC3801203 | biostudies-literature
Project description:Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes. Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the effect of prenatal stress (PNS), an experimental paradigm associated with behavioral and molecular alterations relevant for psychiatric disorders. We identified 138 genes as being differentially methylated in the prefrontal cortex (PFC) and in the hippocampus (HIP) of male and female adult rats exposed to PNS. Among these genes, miR-30a and Neurod1 emerged as potential players for the negative outcomes associated with PNS exposure. Indeed, in addition to showing consistent methylation differences in both brain regions and in both sexes, and interacting with each other, they are both involved in Axon guidance and Neurotrophin signaling, which are important to neurodevelopmental disorders. We also found a significant reduction in the expression of a panel of genes (CAMK2A, c-JUN, LIMK1, MAP2K1, MAP2K2, PIK3CA and PLCG1) that belong to these two biological pathways and are also validated targets of miR-30a, pointing to a down-regulation of these pathways as a consequence of PNS exposure. Interestingly, we also found that miR-30a levels were significantly upregulated in depressed patients exposed to childhood trauma, as compared to control individuals. Importantly, we also found that a sub-chronic treatment with the atypical antipsychotic drug, lurasidone, during adolescence was able to prevent the up-regulation of miR-30a and normalized the expression of its target genes in response to PNS exposure. Our results demonstrate that miR-30a undergoes epigenetic changes following early life stress exposure and suggest that this miRNA could play a key role in producing broad and long-lasting alterations in neuroplasticity-related pathways, contributing to the etiology of psychiatric disorders.
| S-EPMC7739180 | biostudies-literature
Project description:MicroRNAs (miRNAs), one of the major small non-coding RNA classes, have been proposed as regulatory molecules in neurodevelopment and stress response. Although alterations in miRNAs profiles have been implicated in several psychiatric and neurodevelopmental disorders, the contribution of individual miRNAs in brain development and function is still unknown. Recent studies have identified miR-19 as a key regulator of brain trajectories, since it drives the differentiation of neural stem cells into mature neurons. However, no findings are available on how vulnerability factors for these disorders, such as early life stress (ELS), can modulate the expression of miR-19 and its target genes. To reach our aim, we investigated miR-19 modulation in human hippocampal progenitor stem cells (HPCs) treated with cortisol during 3 days of proliferation and harvested immediately after the end of the treatment or after 20 days of differentiation into mature neurons. We also analyzed the long-term expression changes of miR-19 and of its validated target genes, involved in neurodevelopment and inflammation, in the hippocampus of adult rats exposed or not to prenatal stress (PNS). Interestingly, we observed a significant downregulation of miR-19 levels both in proliferating (FC = -1.59, p-value = 0.022 for miR-19a; FC = -1.79, p-value = 0.016 for miR-19b) as well as differentiated HPCs (FC = -1.28, p-value = 0.065 for miR-19a; FC = -1.75, p-value = 0.047 for miR-19b) treated with cortisol. Similarly, we found a long-term decrease of miR-19 levels in the hippocampus of adult PNS rats (FC = -1.35, p-value = 0.025 for miR-19a; FC = -1.43, p-value = 0.032 for miR-19b). Among all the validated target genes, we observed a significant increase of NRCAM (FC = 1.20, p-value = 0.027), IL4R (FC = 1.26, p-value = 0.046), and RAPGEF2 (FC = 1.23, p-value = 0.020).We suggest that ELS can cause a long-term downregulation of miR-19 levels, which may be responsible of alterations in neurodevelopmental pathways and in immune/inflammatory processes, leading to an enhanced risk for mental disorders later in life. Intervention strategies targeting miR-19 may prevent alterations in these pathways, reducing the ELS-related effects.
| S-EPMC7243913 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-21 | GSE189567 | GEO
Project description:Early postnatal-life malnutrition remains prevalent globally, and about 45% of all child deaths are linked to malnutrition. It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance.
| S-EPMC6028108 | biostudies-literature
Project description:Understanding the long term impact of early life seizures (ELS) is of vital importance both for researchers and clinicians. Most experimental studies of how seizures affect the developing brain have drawn their conclusions based on changes detected at the cellular or behavioral level, rather than on intermediate levels of analysis, such as the physiology of neuronal networks. Neurons work as part of networks and network dynamics integrate the function of molecules, cells and synapses in the emergent properties of brain circuits that reflect the balance of excitation and inhibition in the brain. Therefore, studying network dynamics could help bridge the cell-to-behavior gap in our understanding of the neurobiological effects of seizures. To this end we investigated the long-term effects of ELS on local network dynamics in mouse neocortex. By using the pentylenetetrazole (PTZ)-induced animal model of generalized seizures, single or multiple seizures were induced at two different developmental stages (P9-15 or P19-23) in order to examine how seizure severity and brain maturational status interact to affect the brain's vulnerability to ELS. Cortical physiology was assessed by comparing spontaneous network activity (in the form of recurring Up states) in brain slices of adult (>5 mo) mice. In these experiments we examined two distinct cortical regions, the primary motor (M1) and somatosensory (S1) cortex in order to investigate regional differences in vulnerability to ELS. We find that the effects of ELSs vary depending on (i) the severity of the seizures (e.g., single intermittent ELS at P19-23 had no effect on Up state activity, but multiple seizures induced during the same period caused a significant change in the spectral content of spontaneous Up states), (ii) the cortical area examined, and (iii) the developmental stage at which the seizures are administered. These results reveal that even moderate experiences of ELS can have long lasting age- and region-specific effects in local cortical network dynamics.
| S-EPMC6277496 | biostudies-literature