scholarly journals Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception

2020 ◽  
Vol 11 ◽  
Author(s):  
Ahmad Alwazzan ◽  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Shahida Perveen ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Acetylcholine Receptor ◽  
First Trimester ◽  
Sudden Infant ◽  
Tissue Samples ◽  
Acetyl Choline ◽  
Α7 Nachr ◽  
Products Of Conception ◽  
Villous Trophoblast ◽  
Two Samples

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied.Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer.Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi.Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.

Comparative expression of lysyl oxidases in early and late first trimester placentas and their implication in villous trophoblast differentiation

Placenta ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. A109
Author(s):  
Nadine Segond ◽  
Audrey Chissey ◽  
Alicia Grosso ◽  
Jean Guibourdenche ◽  
Bruno Saubamea ◽  
...  
Keyword(s):  
First Trimester ◽  
Trophoblast Differentiation ◽  
Lysyl Oxidases ◽  
Villous Trophoblast

Abstract P242: Nicotinic Acetylcholine Receptor Subunit α7 is Protective Against Angiotensin II-induced Aneurysm and Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Nayaab S Khan ◽  
Spyros Mavropoulos ◽  
Kaie Ojamaa
Keyword(s):  
Blood Pressure ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Low Dose ◽  
Histological Analysis ◽  
Inflammatory Activity ◽  
High Dose ◽  
Ang Ii ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr

Alpha7 nicotinic acetylcholine receptor (α7 nAChR), an integral component of the cholinergic nervous system is known to mediate cholinergic anti-inflammatory activity in various disease models such as sepsis, stroke and neurocognitive disorders. We report for the first time that the α7 nAChR -/- deficient mouse serves as a novel model of hypertension and aneurysm formation. Seven month old male WT and α7 nAChR -/- mice weighing 28-33g were infused with low dose Ang II (350 ng/kg/min) or high dose (700 ng/kg/min) or vehicle for 15 days using mini-osmotic pumps (Alzet, model 2004) implanted subcutaneously. Blood pressure (BP) was recorded on day 0,3,7,10 and 14. Mice were euthanized on day 15. Heart and body weights were measured, histological analysis was performed on the aortas and immune profile of peripheral blood was analyzed by flow cytometry. High dose Ang II resulted in 70% mortality from aneurysm rupture in α7 nAChR -/- mice starting as early as the 4 th day of infusion. While cardiac hypertrophy was not observed, low dose Ang II resulted in a sharp rise in blood pressure in α7 nAChR -/- beginning on the 3 rd day to 167±3.7 mmHg compared to 138±3.3 mmHg in WT treated mice. On day14 of low dose treatment, BP in α7 nAChR -/- rose to 171±4.2 vs.135±3.1 in WT mice. No changes were observed in BP of untreated WT or α7 nAChR -/- animals. Histological analysis revealed high grade aneurysm in aortas of α7 nAChR -/- mice treated with low dose Ang II, demonstrating a prominent germinal center within the false lumen and fibrous desmoplastic stroma. Increased infiltration of CD11B + monocytes, and myeloperoxidase + stained neutrophils were observed in these aortas but not in the aortas of similarly treated WT mice. Flow cytometric analysis showed 27% ± 3.9 CD11B + /CD45 + circulating monocytes and 48% ± 0.8 Ly6G + /CD45 + neutrophils in α7 nAChR -/- vs. 19% ± 3 monocytes and 11.85% ± 2.9 neutrophils in WT mice. No differences in the levels of circulating immune cells were observed in untreated mice of either genotype. These data support a protective role of α7 nAChR in hypertension and aneurysm, potentially acting through its cholinergic anti-inflammatory activity. The α7 nAChR -/- mouse may serve as a new genetic model of aneurysm relevant in studies of the human disease.

Abstract W P98: Activation of α7 Nicotinic Acetylcholine Receptor Reduces Pro-Inflammatory Macrophage and Improves Ischemic Stroke Recovery

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Zhenying Han ◽  
Fanxia Shen ◽  
Yue He ◽  
Vincent Degos ◽  
Marine Camus ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Stroke Recovery ◽  
Behavioral Tests ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Adhesive Removal ◽  
Inflammatory Macrophages

Background and Purpose: Inflammation influences stroke recovery. Activation of α7 nicotinic acetylcholine receptor (α7 nAchR) attenuates inflammation. We hypothesize that α7 nAchR agonist treatment reduces pro-inflammatory macrophages (M1) and improves ischemic stroke recovery. Methods: C57BL/6 mice underwent permanent distal middle cerebral artery occlusion (pMCAO). They were randomly assigned to 7 groups: injected intraperitoneally with 0.4 or 0.8 mg/Kg PHA568487 (PHA, α7 nAchR agonist), 4 or 6 mg/Kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline immediately after pMCAO, or with 0.8 mg/Kg PHA or 6 mg/kg MLA immediately and 24 hours after pMCAO. Behavior was assessed by corner and adhesive removal tests at 3, 7, and 14 days after pMCAO (n=12). Atrophic volume (n=7) and the percentage of total (CD68 + ) and M1 (CD11b + /Iba1 + ) macrophages (n=6) among total cells in the peri-infarct region were quantified 14 days after pMCAO. The expression of M1 (CD11b and iNOS) and M2 marker (CD206) were quantified using real-time RT-PCR (n=4). Results: Compared to the saline-treated mice, those treated with two doses of 0.8 mg/kg PHA performed better in both behavioral tests at 3 (adhesive: p=0.01, corner: p=0.02) and 7 (adhesive: p=0.005, corner: p=0.03) days, and in the adhesive removal test at 14 days (p=0.004) after pMCAO. They had smaller atrophic volume (16±7 mm 3 vs 26±5 mm 3 , p=0.008), and fewer total (9±2.5% vs 15.8±1.7%, p<0.001) and M1 (14±2.3% vs 20.6±4.2%, p=0.005) macrophages. Mice treated with two doses of 6 mg/kg MLA performed worse in the behavioral tests at all times (p<0.05), had larger atrophic volume (48±20 mm 3 , p=0.03), and more total (25±4.2%, p=0.0003) and M1 macrophages (28±4.5%, p=0.01). The expression of CD11b and iNOS decreased (p<0.05) in the PHA group, and increased (p=0.01) in the MLA group. CD206 expression increased (p=0.04) in the PHA group and did not change in the MLA group. One-dose treatment had no effect. Conclusions: Activation of α7 nAchR reduces pro-inflammatory macrophages in the peri-infarct region, which is associated with reduction of atrophic volume and improvement of behavioral recovery.

Abstract 31: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVCs) Show Superior Angiogenic Potential in Angiogenic Potency Assays When Compared to Term HUCPVCs and Bone Marrow Stromal Cells

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Farwah Iqbal ◽  
Peter Szaraz ◽  
Jun Wu ◽  
Andree Gauthier-Fisher ◽  
Ren-Ke Li ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Umbilical Cord ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Aortic Ring ◽  
First Trimester ◽  
Marrow Stromal Cells ◽  
Human Umbilical Cord ◽  
Angiogenic Potential ◽  
Aortic Ring Assay

Introduction: Cell therapy employing pro-angiogenic cell types is a promising option for promoting revascularization of ischemic tissues. First trimester human umbilical cord perivascular cells (FTM HUCPVCs) are a young source of mesenchymal stromal cells (MSCs) that support blood vessels in the umbilical cord. Objective: We aimed to determine the angiogenic potential of FTM HUCPVCs using angiogenic potency assays and compare to older sources of MSCs: term HUCPVCs and bone marrow stromal cells (BMSCs). Methods: For the aortic ring assay, aortas were sectioned and embedded into Matrigel™. Fluorophore-labeled MSCs for testing were added to developing endothelial networks (Day0). MSC integration and network development were monitored by microscopy and quantification of endothelial networks was performed using ImageJ™ software (Day4) n=3. Using the Matrigel™ plug assay, 5.0 x10 5 MSCs were suspended with equal volumes of Matrigel™ and injected subcutaneously in 11-week-old nude mice and isolated after two weeks. Plug associated microvasculature was imaged and quantified n=3. Results: In the aortic ring assay, FTM HUCPVCs homed to endothelial networks and demonstrated greater endothelial cell coverage, when compared to term HUCPVCs and BMSCs. FTM HUCPVCs showed significantly greater network growth when compared to term HUCPVCs ( p ≤0.001), BMSCs ( p ≤0.001) and untreated endothelial networks ( p ≤0.001). FTM HUCPVC contributed to a significantly greater number of closed loops when compared to term HUCPVCs ( p ≤0.01), BMSCs ( p ≤0.001) and untreated networks ( p ≤0.05). At two weeks following injection of Matrigel plugs, FTM HUCPVC resulted in significantly greater blood vessel recruitment when compared to term HUCPVCs ( p ≤0.05), BMSCs ( p ≤0.01) and control media plugs ( p ≤0.01). Small tortuous blood vessels were found in significantly higher quantity in FTM HUCPVC injected plugs when compared to term HUCPVCs ( p ≤0.05), BMSCs (p ≤0.01) and media plugs ( p ≤0.001). Conclusions: These studies demonstrate that FTM HUCPVCs have superior potential to augment, both the initiation of capillary formation and the development of functional, perfusable blood vessels, highlighting their potential for tissue regeneration following ischemic injury.

Detection of retained products of conception following spontaneous abortion in the first trimester.

1991 ◽  
Vol 10 (7) ◽  
pp. 387-395 ◽  
Author(s):  
A B Kurtz ◽  
R D Shlansky-Goldberg ◽  
H Y Choi ◽  
L Needleman ◽  
R J Wapner ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
First Trimester ◽  
Retained Products Of Conception ◽  
Products Of Conception ◽  
Retained Products

scholarly journals In Silico Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype

2020 ◽  
Vol 21 (17) ◽  
pp. 6189
Author(s):  
Kuntarat Arunrungvichian ◽  
Sumet Chongruchiroj ◽  
Jiradanai Sarasamkan ◽  
Gerrit Schüürmann ◽  
Peter Brust ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
In Silico ◽  
Amino Acid Residues ◽  
Nicotinic Acetylcholine ◽  
Selective Binding ◽  
Ligand Selectivity ◽  
Α7 Nachr ◽  
Nachr Subtype

The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47–327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the α7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.

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