Irs2 deficiency alters hippocampus-associated behaviors during young adulthood.
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ABSTRACT:
SUBMITTER: Tanokashira D
PROVIDER: S-EPMC8361845 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study aimed at assessing developmental trajectories of risk behaviors from adolescence into young adulthood and their associations with outcomes in young adulthood (i.e. education, employment). Data of the TRacking Adolescents' Individual Lives Survey (TRAILS) including 2,149 participants (mean age = 13.6, SD = 0.5, 51% girls) were used to examine the development of alcohol, cannabis, smoking, and externalizing behavior. The results showed that the associations between these risk behaviors varied with age, and revealed varying developmental patterns throughout adolescence. Most notably alcohol use did not covary strongly with the other risk behaviors. The often assumed peak in risk behavior in adolescence was only found in a small group, and only for alcohol (7.4%) and cannabis use (3.4%), but not for smoking or externalizing behavior. Most adolescents revealed only low involvement in risk behavior, with the largest differences between low and high trajectories emerging in late adolescence (> 19 years). Clustering of risk behavior throughout adolescence is rather the exception than the rule and depends on age and type of risk behavior. Differences in risk behavior between individuals become the largest in late adolescence, possibly influencing successful transition into adulthood visible in educational attainment and employment.
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Project description:Well-liked adolescents are more likely than their peers to engage in sexual behaviors, which may place them at higher risk of negative outcomes such as sexually transmitted infections and unwanted pregnancy. Yet, little is known regarding whether peer acceptance in adolescence predicts sexual outcomes in young adulthood. Understanding developmental links between peer acceptance and sexual outcomes will inform theories of how peers affect health and can help identify targets for health promotion efforts. Using longitudinal sociometric data from 1878 participants in the PROSPER study (54% female, 82% White, mean age?=?11.79 at baseline), the present research examined the association of adolescent peer acceptance, reported annually from grades 6-11, with adolescent and young adult sexual outcomes. Well-liked adolescents were more likely to have sexual intercourse by age 16. At age 19, well-liked individuals were more likely to have had sexual intercourse but were less likely to be diagnosed with a sexually transmitted infection. For boys but not girls, peer acceptance was linked to having more past year sexual partners in young adulthood. Adolescent peer acceptance was not associated with other young adult sexual outcomes, such as sex without a condom or casual sex. Overall, well-liked adolescents demonstrated healthy sexual development into young adulthood, despite a higher likelihood of sexual initiation early in adolescence. Findings demonstrate the importance of peer acceptance for healthy development into young adulthood and suggest that well-liked adolescents may be appropriate targets for peer-led sexual health education programs.
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Project description:We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hippocampus (p < 0.01 vs. CT and CS), with no change in total cross-sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0-fold, p < 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1-fold, (p < 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 microM), CT (70 microM), or high choline (280 microM) media for 72 h (low choline caused a 9.7-fold increase in relative gene expression of Vegfc (p < 0.001 vs. CT and high) and a 3.4-fold increase in expression of Angpt2, (p < 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p < 0.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas of Vegfc and Angpt2 were hypomethylated in low choline NPC compared to CT NPC (p < 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.
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Project description:Using data from three waves of the National Longitudinal Study of Adolescent Health (N=4,538), we examine the intergenerational link between parental family structure history and relationship formation in young adulthood. We investigate: (a) first, whether parental family structure history is associated with young adults' own relationship formation behaviors; (b) second, which dimensions of family structure history are most predictive of children's later relationship formation behaviors; and (c) third, if the association between family structure history and young adulthood relationship formation differs by gender. Our findings provide evidence of an intergenerational link between parent relationship histories and their offspring's own relationship formation behaviors in young adulthood, over and above confounding factors.
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Project description:Insulin receptor substrate 2 (IRS2) is a key downstream mediator of insulin and insulin-like growth factor 1 (IGF1) signalling pathways and plays a major role in liver metabolism. The aim of this study was to investigate whether IRS2 had an impact on the hepatic fibrotic process associated with cholestatic injury. Bile duct ligation (BDL) was performed in wild-type (WT) and Irs2-deficient (IRS2KO) female mice. Histological and biochemical analyses, together with fibrogenic and inflammatory responses were evaluated in livers from mice at 3, 7 and 28 days following BDL. We also explored whether activation of human hepatic stellate cells (HSCs) induced by IGF1 was modulated by IRS2. IRS2KO mice displayed reduced disruption of liver histology, such hepatocyte damage and excess deposition of extracellular matrix components, compared with WT mice at 3 and 7 days post-BDL. However, no histological differences between genotypes were found at 28 days post-BDL. The less pro-inflammatory profile of bile acids accumulated in the gallbladder of IRS2KO mice after BDL corresponded with the reduced expression of pro-inflammatory markers in these mice. Stable silencing of IRS2 or inhibition of ERK1/2 reduced the activation of human LX2 cells and also reduced induction of MMP9 upon IGF1 stimulation. Furthermore, hepatic MMP9 expression was strongly induced after BDL in WT mice, but only a slight increase was found in mice lacking IRS2. Our results have unravelled the signalling pathway mediated by IGF1R-IRS2-ERK1/2-MMP9 as a key axis in regulating HSC activation, which might be therapeutically relevant for targeting liver fibrosis.
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Project description:Obese women have a higher risk of developing endometrial cancer (EC) than lean women. Besides affecting EC progression, obesity also affects sensitivity of patients to treatment including medroxprogesterone acetate (MPA). Obese women have a lower response to MPA with an increased risk for tumor recurrence. While MPA inhibits the growth of normal fibroblasts, human endometrial cancer-associated fibroblasts (CAFs) were reported to be less responsive to MPA. However, it is still unknown how CAFs from obese women respond to progesterone. CAFs from the EC tissues of obese (CO) and non-obese (CN) women were established as primary cell models. MPA increased cell proliferation and downregulated stromal differentiation genes, including BMP2 in CO than in CN. Induction of IRS2 (a BMP2 regulator) mRNA expression by MPA led to activation of glucose metabolism in CO, with evidence of greater mRNA levels of GLUT6, GAPDH, PKM2, LDHA, and increased in GAPDH enzymatic activity. Concomitantly, MPA increased the mRNA expression of a fatty acid transporter, CD36 and lipid droplet formation in CO. MPA-mediated increase in glucose metabolism genes in CO was reversed with a progesterone receptor inhibitor, mifepristone (RU486), leading to a decreased proliferation. Our data suggests that PR signaling is aberrantly activated by MPA in CAFs isolated from endometrial tissues of obese women, leading to activation of IRS2 and glucose metabolism, which may lead to lower response and sensitivity to progesterone in obese women.
| S-EPMC9273069 | biostudies-literature
Project description:UnlabelledIron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2(hipp/hipp) mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2(hipp/hipp) mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2(hipp/hipp) mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems.Electronic supplementary materialThe online version of this article (doi:10.1007/s11689-010-9049-0) contains supplementary material, which is available to authorized users.
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Project description:ObjectivesAn Antisocial Behavior index (ASB-I) for children (ages 5 to 15) was previously developed by obtaining clinician ratings of the seriousness or severity of various behaviors with the goal of improving assessment of antisocial behaviors (ASB) longitudinally. We extend the instrument for use in late adolescence/young adulthood, as socially unacceptable conduct manifests differently across developmental stages. As in the original study, this extension (the ASB-I YA) is based on independent ratings of ASB seriousness/severity during late adolescence/young adulthood (16 to 28 years) made by nine experienced clinicians.MethodsThe items rated were drawn from the Oppositional Defiant Disorder and Conduct Disorder schedules of the NIMH Diagnostic Interview Schedule for Children (DISC-IV) and the Elliott Delinquency scales, plus new or modified items developmentally appropriate for late adolescence/young adulthood. Specific ratings were based on the developmental stage and reported frequency of the behaviors. The study also describes the distribution of ASB-I YA scores in the Boricua Youth Study.ResultsReliability was substantial for the average ratings of each subscale and for the total score [ICC(3,9): .88 to .95]. Certain items were rated as more severe when occurring in late adolescence/young adulthood compared to childhood/early adolescence (e.g., hitting someone on purpose); however, most ratings were similar across developmental periods. Most importantly, raters reliably and consistently rated the items describing ASB in young adulthood, allowing the computation of the ASB-I YA score.ConclusionsTogether with the ASB-I, the ASB-I YA can further advance the study of ASB progression from childhood into young adulthood.
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Project description:Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of alcohol use, drinking to the point of drunkenness, smoking, cannabis use, deviance, and HIV-related sexual risk behavior were compared in a Swiss community sample (N = 2,843). Using a longitudinal cohort-sequential approach to link multiple assessments with 3 waves of data for each individual, the studied period spanned the ages of 16 to 29 years. Although smoking had a higher prevalence, both smoking and drinking up to the point of drunkenness followed an inverted U-shaped curve. Alcohol consumption was also best described by a quadratic model, though largely stable at a high level through the late 20s. Sexual risk behavior increased slowly from age 16 to age 22 and then remained largely stable. In contrast, cannabis use and deviance linearly declined from age 16 to age 29. Young men were at higher risk for all behaviors than were young women, but apart from deviance, patterning over time was similar for both sexes. Results about the timing of increase and decline as well as differences between risk behaviors may inform tailored prevention programs during the transition from late adolescence to adulthood.
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Project description:How to mitigate the dramatic increase in the number of self-inflicted deaths from suicide, alcohol-related liver disease, and drug overdose among young adults has become a critical public health question. A promising area of study looks at interventions designed to address risk factors for the behaviors that precede these -often denoted-"deaths of despair." This paper examines whether a childhood intervention can have persistent positive effects by reducing adolescent and young adulthood (age 25) behaviors that precede these deaths, including suicidal ideation, suicide attempts, hazardous drinking, and opioid use. These analyses test the impact and mechanisms of action of Fast Track (FT), a comprehensive childhood intervention designed to decrease aggression and delinquency in at-risk kindergarteners. We find that random assignment to FT significantly decreases the probability of exhibiting any behavior of despair in adolescence and young adulthood. In addition, the intervention decreases the probability of suicidal ideation and hazardous drinking in adolescence and young adulthood as well as opioid use in young adulthood. Additional analyses indicate that FT's improvements to children's interpersonal (e.g., prosocial behavior, authority acceptance), intrapersonal (e.g., emotional recognition and regulation, social problem solving), and academic skills in elementary and middle school partially mediate the intervention effect on adolescent and young adult behaviors of despair and self-destruction. FT's improvements to interpersonal skills emerge as the strongest indirect pathway to reduce these harmful behaviors. This study provides evidence that childhood interventions designed to improve these skills can decrease the behaviors associated with premature mortality.
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