scholarly journals Effect of PM2.5 Exposure On Gestational Hypertension and Fetal Size in Preeclampsia-Like Rats

2021 ◽  
Author(s):  
Jie Gao ◽  
Mei Luo ◽  
Shuo Zhao ◽  
Hailing Wang ◽  
Xuan Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Th17 Cells ◽  
Gestational Hypertension ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Mrna And Protein Expression ◽  
Fetal Size ◽  
Adverse Pregnancy

Abstract Studies have reported that gestational PM2.5 exposure is associated with preeclampsia (PE) and fetal growth restriction (FGR). However, whether maternal exposure to PM2.5 causes adverse pregnancy outcomes is still largely unknown. Pregnant Sprague-Dawley rats were exposed to either filtered (FA) or PM2.5 air during the whole pregnant period. A PE-like rat model was established by intraperitoneal injection of L-NAME (300 mg/kg) from GD12 to until GD20. Systolic blood pressure (SBP), weight gain, pup weight and placental weight were measured. The percentages of rat Treg/Th17 cells and Th17-related cytokines were examined by flow cytometry. Gene expression profiles were analyzed by microarray, and the expression of differentially expressed genes were validated by qRT-PCR. The results showed that maternal PM2.5 exposure had no effect on SBP but was associated with LBW and a higher labyrinth/basal zone ratio. The percentages of splenic Th17 cells from the PM2.5 group in PE-like rats were higher than those from the FA or PM2.5 groups in healthy controls. A significantly decreased Treg/Th17 cell ratio was found in the PM2.5 group in PE-like rats. The mRNA expression of Foxp3 was downregulated, while the mRNA expression of RORα and RORγτ was upregulated after PM2.5 exposure. Furthermore, we observed that both the mRNA and protein expression of TNF-a, CCL2, CCL3 and CCR1 increased in the PM2.5 groups. Our study suggested that systemic inflammation may contribute to the development of FGR associated with PM2.5 exposure throughout pregnancy.

scholarly journals Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function

2020 ◽  
Author(s):  
Marcus Garcia ◽  
Raul Salazar ◽  
Thomas Wilson ◽  
Selita Lucas ◽  
Guy Herbert ◽  
...  
Keyword(s):  
Uterine Artery ◽  
Gestational Hypertension ◽  
Resistance Index ◽  
Cardiovascular Effects ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Transcriptional Changes ◽  
Adverse Pregnancy ◽  
Underlying Mechanisms

Abstract Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

scholarly journals Using rat operant delayed match-to-sample task to identify neural substrates recruited with increased working memory load

2020 ◽  
Author(s):  
Christina Gobin ◽  
Lizhen Wu ◽  
Marek Schwendt
Keyword(s):  
Working Memory ◽  
Mrna Expression ◽  
Memory Load ◽  
Neural Substrates ◽  
High Load ◽  
Limited Information ◽  
Sprague Dawley ◽  
Match To Sample ◽  
Sprague Dawley Rats ◽  
Subcortical Regions

AbstractThe delayed match-to-sample task (DMS) is used to probe working memory (WM) across species. While the involvement of the PFC in this task has been established, limited information exists regarding the recruitment of broader circuitry, especially under the low- versus high-WM load. We sought to address this question by using a variable-delay operant DMS task. Male Sprague-Dawley rats were trained and tested to determine their baseline WM performance across all (0-24s) delays. Next, rats were tested in a single DMS test with either 0s or 24s fixed delay, to assess low-/high-load WM performance. c-Fos mRNA expression was quantified within cortical and subcortical regions and correlated with WM performance. High WM load upregulated overall c-Fos mRNA expression within the PrL, as well as within a subset of mGlu5+ cells, with load-dependent, local activation of protein kinase C as the proposed underlying molecular mechanism. The PrL activity negatively correlated with choice accuracy during high load WM performance. A broader circuitry, including several subcortical regions, was found to be activated under low and/or high load conditions. These findings highlight the role of mGlu5 and/or PKC dependent signaling within the PrL, and corresponding recruitment of subcortical regions during high-load WM performance.

scholarly journals Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion

2017 ◽  
Vol 49 (1) ◽  
pp. 37-52 ◽  
Author(s):  
Ahmed S. Bux ◽  
Merry L. Lindsey ◽  
Hernan G. Vasquez ◽  
Heinrich Taegtmeyer ◽  
Romain Harmancey
Keyword(s):  
Heart Surgery ◽  
Expression Profiles ◽  
Macrophage Polarization ◽  
Open Heart Surgery ◽  
Gene Expression Profiles ◽  
Metabolic Reprogramming ◽  
Open Heart ◽  
Sprague Dawley ◽  
Proinflammatory Mediators ◽  
Perfused Hearts

We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were cold-arrested in Krebs-Henseleit buffer and subjected to 60 min normothermic reperfusion in the working mode with buffer supplemented with noncarbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared with those of nonperfused hearts. Perfused hearts displayed a transcriptional signature independent from the presence of glucose showing a more than twofold increase in expression of 71 genes connected to inflammation, cell proliferation, and apoptosis. These transcriptional alterations were very similar to the ones taking place in the hearts of open heart surgery patients. Prominent among those alterations was the upregulation of the three master regulators of metabolic reprogramming, MYC, NR4A1, and NR4A2. Targeted pathway analysis revealed an upregulation of metabolic processes associated with the proliferation and activation of macrophages and fibroblasts. Glucose potentiated the upregulation of a subset of genes associated with polarization of tissue reparative M2-like macrophages, an effect that was lost in perfused hearts from rats rendered insulin resistant by high-sucrose feeding. The results expose the heart as a significant source of proinflammatory mediators released in response to stress associated with cardiac surgery with cardiopulmonary bypass, and suggest a major role for glucose as a signal in the determination of resident cardiac macrophage polarization.

Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles

2000 ◽  
Vol 89 (4) ◽  
pp. 1483-1490 ◽  
Author(s):  
William G. Schrage ◽  
Christopher R. Woodman ◽  
M. Harold Laughlin
Keyword(s):  
Sodium Nitroprusside ◽  
Group Treatment ◽  
Day Treatment ◽  
Weight Bearing ◽  
Immunoblot Analysis ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Protein Levels ◽  
Sprague Dawley Rats ◽  
Mrna And Protein Expression

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10−9–10−4 M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10−9–10−4 M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 ± 4 and 121 ± 4 μm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 ± 3 and 45 ± 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats ( P = 0.03), as was maximal dilation to ACh (85 ± 4 and 65 ± 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with N ω-nitro-l-arginine (300 μM) reduced ACh dilation by ∼40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 μM) did not significantly alter dilation to ACh in either group. Treatment with N ω-nitro-l-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups ( P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.

Effect of exercise on mRNA expression of select adrenal medullary catecholamine biosynthetic enzymes

2002 ◽  
Vol 93 (2) ◽  
pp. 463-468 ◽  
Author(s):  
S. Remzi Erdem ◽  
Haydar A. Demirel ◽  
Christopher S. Broxson ◽  
Bistra B. Nankova ◽  
Esther L. Sabban ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Mrna Expression ◽  
Protein Level ◽  
Binding Activity ◽  
Biosynthetic Enzymes ◽  
Sprague Dawley ◽  
Training Set ◽  
Sprague Dawley Rats ◽  
Sympathoadrenal Activity ◽  
Th Mrna

The effect of submaximal endurance training (SET) on sympathoadrenal activity is not clear. We tested the hypothesis that SET (90 min/day, 5 days/wk, for 12 wk) elevates mRNA expression of catecholamine (CA) biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH) in the adrenal medullae of adult, female Sprague-Dawley rats. SET increased TH protein level by 35%, TH activity by 62%, TH mRNA expression by 40%, and DβH mRNA expression by 67%. In addition, we examined the effect of SET on Fos-related antigens (FRAs), FRA-2 immunoreactivity, and activator protein (AP)-1 binding activity. SET increased AP-1 binding activity by 78%; however, it did not affect late FRAs and FRA-2 immunoreactivity. Because the regulation of neuropeptide Y (NPY) often parallels that of CAs, we also examined the effect of SET on NPY mRNA expression. Indeed, SET elevated NPY mRNA expression as well. We conclude that 1) SET elicits a pretranslational stimulatory effect on adrenomedullary CA biosynthetic enzymes, 2) another immediate early mRNA product, rather than FRA-2, may contribute to the increase in AP-1 binding activity in response to SET, and 3) SET increases NPY mRNA expression.

scholarly journals Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
J. Ruth Wu-Wong ◽  
Masaki Nakane ◽  
Gerard D. Gagne ◽  
Kristin A. Brooks ◽  
William T. Noonan
Keyword(s):  
Vitamin D ◽  
Cell Proliferation ◽  
Mrna Expression ◽  
Active Form ◽  
Parathyroid Cell ◽  
Pharmacological Effects ◽  
Sprague Dawley ◽  
Mineral Homeostasis ◽  
Sprague Dawley Rats ◽  
Serum Pth

Vitamin D receptor agonists (VDRAs) directly suppress parathyroid hormone (PTH) mRNA expression. Different VDRAs are known to have differential effects on serum calcium (Ca), which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the Ca-sensing receptor (CaSR). In this study, we compared the effects of paricalcitol and doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR mRNA. The 5/6 nephrectomized (NX) Sprague-Dawley rats on a normal or hyperphosphatemia-inducing diet were treated with vehicle, paricalcitol, or doxercalciferol for two weeks. Both drugs at the tested doses (0.042–0.33 g/kg) suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol. In pig parathyroid cells, paricalcitol and the active form of doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH mRNA expression and inhibited cell proliferation in a similar manner, although paricalcitol induced the expression of CaSR mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH mRNA reflect the complex involvement of the vitamin D axis in regulating the mineral homeostasis system.

scholarly journals Pre-existing hypertension and pregnancy induced hypertension reveal molecular differences in placental proteome in rodents

2021 ◽  
Author(s):  
Sheon Mary ◽  
Heather Small ◽  
Florian Herse ◽  
Emma Carrick ◽  
Arun Flynn ◽  
...  
Keyword(s):  
Gestational Hypertension ◽  
Tissue Injury ◽  
Cardiovascular Complications ◽  
Trophoblast Invasion ◽  
Future Research ◽  
Chronic Hypertension ◽  
Label Free ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats

Pre-existing or new onset of hypertension affects pregnancy and is one of the leading causes of maternal and fetal morbidity and mortality. In certain cases, it also leads to long term maternal cardiovascular complications. The placenta is a key player in the pathogenesis of complicated hypertensive pregnancies, however the pathomechanisms leading to an abnormal placenta are poorly understood. In this study we compared the placental proteome of two rat models: a pre-existing hypertension pregnancy model (stroke-prone spontaneously hypertensive, SHRSP) and the transgenic RAS activated gestational hypertension model (transgenic for human angiotensinogen Sprague-Dawley rats, SD-PE). Label-free proteomics using nano LC-MS/MS was performed for identification and quantification of proteins. Between the two models, we found widespread differences in the expression of placental proteins including those related to hypertension, inflammation and trophoblast invasion; whereas pathways such as regulation of serine endopeptidase activity, tissue injury response, coagulation and complement activation were enriched in both models. We present for the first time the placental proteome of SHRSP and SD-PE and provide insight into the molecular make-up of models of hypertensive pregnancy. Our study informs future research into specific preeclampsia and chronic hypertension pregnancy mechanisms and translation of rodent data to the clinic.

scholarly journals Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague–Dawley rats

2021 ◽  
Vol 29 (5) ◽  
pp. 1475-1486
Author(s):  
Jae In Jung ◽  
Hyun Sook Lee ◽  
Young Eun Jeon ◽  
So Mi Kim ◽  
Su Hee Hong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Acid Amide ◽  
Treatment Strategies ◽  
Leukotriene B4 ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Monosodium Iodoacetate ◽  
Anti Inflammatory

AbstractNovel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague–Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

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