11 research outputs found
Placental <i>SLC6A4</i> mRNA levels according to maternal glucose tolerance status and <i>5-HTTLPR</i>/<i>rs25531</i> genotype.
<p>Shown are means and standard errors. p-values were 0.007, 0.316, and 0.176 for the main effect of diagnosis, main effect of genotype, and genotype x diagnosis interaction, respectively (two-way ANOVA). GDM, gestational diabetes mellitus; NGT, normal glucose tolerance; RER; relative expression ratio.</p
Placental <i>SLC6A4</i> methylation levels correlate with maternal fasting glucose concentrations and placental <i>SLC6A4</i> mRNA levels.
<p>Scatterplots depict correlation of placental <i>SLC6A4</i> methylation with (A) maternal fasting glucose levels in the 24th to 28th week of pregnancy, and (B) placental <i>SLC6A4</i> mRNA levels. n, number of subjects; r<sub>p</sub>, Pearson's correlation coefficient; r<sub>s</sub>, Spearman's correlation coefficient; RER, relative expression ratio.</p
Characteristics of newborns and their mothers stratified according to mother's glucose tolerance status.
<p>Characteristics of newborns and their mothers stratified according to mother's glucose tolerance status.</p
Association of placental <i>SLC6A4</i> methylation with categorical variables of the study population.
<p>Association of placental <i>SLC6A4</i> methylation with categorical variables of the study population.</p
Bone biomarkers and hormones in high-5HT and low-5HT rats.
<p>Depicted are relative differences (%): for the overall difference between the high-5HT (H) and low-5HT (L) sublines, P<0.05 is considered significant; for contrasts between sublines at a given age and between different ages within the same subline, P<0.025 is considered significant (n = 5â10 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12â2 indicates a difference between 12 months and 2 months old animals.</p
Systemic role of the peripheral 5HT.
<p>Gut synthesized 5HT enters the platelets via the 5HTT. The quantity of 5HT in platelets depends on the 5HTT activity, while the rate of 5HT synthesis in the gut is equal between both rat sublines (â sign). Changes in the serum Ca<sup>2+</sup> level, influenced by PTH from parathyroid glands and by 1,25(OH)<sub>2</sub>D<sub>3</sub> from the kidney, impact the platelet 5HTT activity, with a bidirectional effect on PSL (green-red arrow). Elevated 5HT bidirectionally influences the plasma insulin level (green-red arrow) and induces the hyperthrophy of pancreatic ÎČ-cells (dashed arrow), leading to type 2 diabetes with an increased plasma glucose, insulin resistance, glucose intolerance, visceral fat volume and decreased muscle strength. In return, plasma insulin level positively correlates with the PSL (+ sign). Increased insulin and 5HT have an additive effect on bone formation (green arrow). Elevated 5HT increases both bone formation and resorption (larger green arrow), thus increasing the bone turnover and resulting in the net bone loss (large red arrow). 5HTâserotonin, 5HTTâserotonin transporter, PSLâplasma serotonin level, PTHâparathyroid hormone.</p
Physiological characteristics of rats from high-serotonin (5HT) and low-5HT sublines.
<p>A. Indicators of 5HT homeostasis shown as âfold differenceâ between high- and low-5HT animals with 95% confidence intervals. Reference values were (mean±SD): a) for platelet serotonin level (PSL) 0.80±0.08 ÎŒg 5HT/mg platelet protein; b) for platelet serotonin uptake (PSU) 0.69±0.07 nmol 5HT/mg platelet protein/min. Rats were 2 months (PSU measurements) and 12 months (gut <i>Mao-A</i>, <i>Tph1</i> and <i>5HTT</i> expression) of age. PSL and gut 5HT turnover data are given for animals of 2 and 12 months of age. B. No difference in 5HT production and storage in the gut was observed between high- and low-5HT rat sublines. 5HT visualized by using immunohistochemistry was documented at 40Ă magnification and is depicted by black arrows. C-E. Physical characteristics of high-5HT and low-5HT animals (mean±SD). High-5HT animals are represented by black squares, low-5HT animals by open circles. Câbody weight; Dâfemur length; Eâhanging time in the string test (mean values from three 60-sec trials separated by 10-min intervals). Relative differences (%) are shown for subline*age interaction contrasts. P-values were adjusted for multiple comparisons (n = 6â15 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12â2 indicates a difference between 12 months and 2 months old animals. Mao-Aâmonoamine oxidase A; Tph1 âtryptophan hydroxylase 1; 5HTTâserotonin transporter</p
3D model of trabecular bone reconstructed from ÎŒCT images for lumbar spine and distal femur in high-5HT and low-5HT rats at 2 and 12 months of age.
<p>A. SpineâÎŒCT images. B-D. Spineâmorphometric indices (mean±SD). E. FemurâÎŒCT images. F-H. Femurâmorphometric indices (mean±SD). Shown are relative differences (%): H-L (high-5HT vs. low-5HT animals) at different age; 12â2 months for high and low 5HT animals (n = 8â14 rats/group). Depicted are relative differences (%): for the overall difference between the high-5HT and low-5HT sublines, P<0.05 is considered significant; for contrasts between sublines at a given age and between different ages within the same subline, P<0.025 is considered significant.</p
<i>In vivo</i> effects of <i>Tph1</i> inhibition on platelet serotonin levels (PSL) and bone parameters in 12 months old high 5-HT subline.
<p>On day 1 of the experiment, PSL was measured and treatment with LX1032 (25 mg/kg) (n = 7) or vehicle (control, n = 6) was commenced. At the last day of treatment (Day 36), PSL was determined again. Animals were sacrificed 24 h after the last dose and bone volume (BV/TV, %), trabecular spacing (TbSp, mm) and number of trabecules (Tb.N, 1/mm) were determined in the femur and spine using ΌCT. A. Data are geometric means (±geometric SD) of PSL values on Day 1 and Day 36. A general linear mixed model (treatment, day [random], treatment*day interaction) was fitted to ln(PSL) and differences (expressed as percentages derived from geometric means ratios) were determined: a) in PSL between the two groups on days 1 and 36; b) in PSL between days 36 and 1, within each group; c) in change in PSL from Day 1 to Day 36 (interaction term coefficient) between the two groups. Adjustment for multiple comparisons was by the simulation method. B. Data are means (±SD) by bone parameter by group, separately for the femur and spine. A separate general linear model was fitted to each of the six ln-transformed outcomes. Differences between groups are expressed as percentage differences (derived from geometric means ratios). C. Non-parametric (Kendall's) regression of bone parameters on change in PSL from the start to the end of treatment. Data depict median slope with confidence interval, Kendall's tau coefficient and P-value.</p