| 1. |
- Jabbari Shiadeh, Seyedeh Marziyeh, et al.
(författare)
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Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring
- 2024
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Ingår i: JOURNAL OF NEUROINFLAMMATION. - 1742-2094. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell-cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice.MethodsMaternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry.ResultsVolume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower.ConclusionMaternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature-glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.
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| 2. |
- Jansson, Thomas, et al.
(författare)
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Business Education and Portfolio Returns
- 2022
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Ingår i: SSRN Electronic Journal. - : SSRN. - 1556-5068 .- 1556-5068.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We provide evidence of a positive causal link between financial knowledge acquired through business education and returns on stock investments. Using exogenous variation generated by admission thresholds to university business programs in Sweden, we document that early investments in financial sophistication causes individuals to invest significantly more in the stock market, to earn higher portfolio returns, and to end up accumulating higher levels of wealth. Investments in financial sophistication at the launch of economic life thus significantly alters the life cycle wealth profiles of individuals
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| 3. |
- Funehag, Johan, et al.
(författare)
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Rock Excavation Cycle and Its Effect on Grouting
- 2019
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Ingår i: ISRM 9th Nordic Grouting Symposium. - : International Society for Rock Mechanics and Rock Engineering. - 9789517586481 ; , s. 47-59
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The drill and blast rock excavation cycle involves several processes that affects the grouting; vibration from drilling, borehole flushing, the blasting itself and water-loss measurements in boreholes. This research project focused on the effects of water-loss measurements, drilling (both vibration and flushing) and blasting on the grout and during the first five hours of the hardening process. A conceptual model was derived to explain what forces acts on the grout and how the forces can be interpreted in order to reveal how these forces effects the grout. The model suggests that the shear modulus of the grout is a key parameter for understanding the degradation of the grout. The different forces/stresses during an excavation effects the grout differently but the blasting is by far the most difficult process to describe. One starting point of the project is that the grout does not reinforce the rock and by that should not hinder the gas expansion. The blasting should generate new fractures around the blast hole and the gas will penetrate these cracks and finally the expansion of gases should cause fragmentation and movement in the rock mass. The paper describes the results from the field test and how the grout has been characterized using a rheometer. The field test was conducted in a short tunnel niche. The effects from the drill- and blast cycle were studied i.e. vibrations from drilling, boreholes flushing/water-loss measurements and vibrations from blasting. Five boreholes with a centrum distance of 1 m were chosen to be monitored, due to its hydraulic connectivity between the boreholes. Four of these boreholes were successfully grouted by following a grouting design and one borehole was left un-grouted and used for blasting. The effect on grouting in the rock mass from hole of blasting was measured using water-loss measurements in adjacent boreholes. One result of the field test is that the grout was not affected by the blasting under the circumstances used. Instead the study revealed that the water loss measurements affected the connected boreholes negatively.
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| 4. |
- Hu, Min, et al.
(författare)
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Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring.
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 112:46, s. 14348-53
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Tidskriftsartikel (refereegranskat)abstract
- During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.
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| 5. |
- Jansson, Nina, 1976, et al.
(författare)
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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies.
- 2013
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:1, s. 105-13
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Tidskriftsartikel (refereegranskat)abstract
- Context: Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown. Objective: We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women. Design and Setting: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. Patients or Other Participants: Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes. Results: Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001). Conclusions: Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
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| 6. |
- Sun, Miao, et al.
(författare)
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Maternal androgen excess reduce placental and fetal weights, increase placental steroidogenesis and leads to long-term health effects in their female offspring.
- 2012
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 303:11
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Tidskriftsartikel (refereegranskat)abstract
- Here we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg free testosterone from gestational day 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptors α and ß, androgen receptor, and 17 beta-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of non-alcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction, however at 6 weeks of age there was no difference in body weight between the offspring of testosterone-, and control-treated rats. At 10-11 weeks of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams and they developed non-alcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.
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| 7. |
- Lager, Susanne, 1978, et al.
(författare)
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Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells.
- 2011
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 32:2, s. 121-7
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Tidskriftsartikel (refereegranskat)abstract
- Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.
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| 8. |
- Sahlstrand Johnson, Pernilla, et al.
(författare)
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IN VITRO STUDIES AND SAFETY ASSESSMENT OF DOPPLER ULTRASOUND AS A DIAGNOSTIC TOOL IN RHINOSINUSITIS
- 2010
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629. ; 36:12, s. 2123-2131
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Tidskriftsartikel (refereegranskat)abstract
- We have previously proposed the use of Doppler ultrasound to noninvasively stage a sinus infection. In this study, we first investigated the acoustic properties of nonpurulent and mucopurulent sinus secretions. The density, viscosity, speed of sound and attenuation of 18 samples of sinus fluid were examined. We then assessed the safety of the method by determining the temperature increase when ultrasound is transmitted through a bone sample of the same thickness as the anterior wall of the maxillary sinus. As a measure of the probability to generate acoustic streaming, we determined the ratio of sound attenuation over the viscosity of the sinus fluid and compared this with the value obtained from acoustic streaming measurements on a model system. The results indicated that detectable levels of acoustic streaming can be generated in serous sinus fluid, which has a low viscosity, but is very unlikely in mucopurulent secretions. The attenuation of the mucopurulent sinus fluid was 10 times higher than that of the serous cyst fluid, but the viscosity of the mucopurulent secretion was a thousand times higher than that of serous fluid. The safety experiments gave a temperature increase of the bone of
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