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- Edman, S., et al.
(författare)
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TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner
- 2012
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 63:3, s. 441-449
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Tidskriftsartikel (refereegranskat)abstract
- Antagonists that are sufficiently selective to preferentially block GluN2A-containing N-methyl-D-aspartate receptors (NMDARs) over GluN2B-containing NMDARs are few in number. In this study we describe a pharmacological characterization of 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulphonamide (TCN 201), a sulphonamide derivative, that was recently identified from a high-throughput screen as a potential GluN2A-selective antagonist. Using two-electrode voltage-clamp (TEVC) recordings of NMDAR currents from Xenopus laevis oocytes expressing either GluN1/GluN2A or GluN1/GluN2B NMDARs we demonstrate the selective antagonism by TCN 201 of GluN2A-containing NMDARs. The degree of inhibition produced by TCN 201 is dependent on the concentration of the GluN1-site co-agonist, glycine (or D-serine), and is independent of the glutamate concentration. This GluN1 agonist-dependency is similar to that observed for a related GluN2A-selective antagonist, N-(cyclohexylmethyl)-2[{5-[(phenylmethyl)amino]-1,3,4-thiadiazol-2-yl}thio]acetamide (TCN 213). Schild analysis of TCN 201 antagonism indicates that it acts in a non-competitive manner but its equilibrium constant at GluN1/GluN2A NMDARs indicates TCN 201 is around 30-times more potent than TCN 213. In cortical neurones TCN 201 shows only modest antagonism of NMDAR-mediated currents recorded from young (DIV 9-10) neurones where GluN2B expression predominates. In older cultures (DIV 15-18) or in cultures where GluN2A subunits have been over-expressed TCN 201 gives a strong block that is negatively correlated with the degree of block produced by the GluN2B-selective antagonist, ifenprodil. Nevertheless, while TCN 201 is a potent antagonist it must be borne in mind that its ability to block GluN2A-containing NMDARs is dependent on the GluN1-agonist concentration and is limited by its low solubility. (C) 2012 Elsevier Ltd. All rights reserved.
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| 2. |
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| 3. |
- Larsson, C., et al.
(författare)
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Factors independently related to a negative birth experience in first-time mothers
- 2011
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 2:2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the impact of personality, socio-demographic and obstetric factors on birth experience in a cohort of healthy first-time mothers. A second aim was to compare a visual analogue scale and Wijma Delivery Experience Questionnaire B as instruments evaluating birth experience. Material and methods: In total, 541 women were prospectively followed from the end of pregnancy until 9 months postpartum. Socio-demographic, psychological and somatic data as well as personality characteristics were collected. Experience of delivery was measured with a visual analogue scale and with Wijma Delivery Experience Questionnaire B. Sixty-three variables were considered to be associated with the experience of delivery. Nineteen of these, found to be significantly associated with birth experience, were entered in a logistic regression analysis. Results: The logistic regression analysis showed that a memory of pain during birth, high usage of analgesics postpartum, long hospital stay, worry in late pregnancy and high self-rated irritation were related to a more negative birth experience, while high confidence in the midwife was related to a more positive experience. The correlation between experiences of delivery rated by Wijma Delivery Experience Questionnaire B and the visual analogue scale was 0.52 (p<0.001). Conclusion: To help women to cope with pain during and after birth could be an important factor to improve birth experience. Even though the correlation between the visual analogue scale and Wijma Delivery Experience Questionnaire B was moderate, the visual analogue scale could be used as a simple method for screening of birth experience. © 2010 Elsevier B.V.
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| 6. |
- Yang, SZ, et al.
(författare)
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Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons
- 2013
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 140:22, s. 4554-4564
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Tidskriftsartikel (refereegranskat)abstract
- CXCL12/CXCR4 signaling has been reported to regulate three essential processes for the establishment of neural networks in different neuronal systems: neuronal migration, cell positioning and axon wiring. However, it is not known whether it regulates the development of A9-A10 tyrosine hydroxylase positive (TH+) midbrain dopaminergic (mDA) neurons. We report here that Cxcl12 is expressed in the meninges surrounding the ventral midbrain (VM), whereas CXCR4 is present in NURR1+ mDA precursors and mDA neurons from E10.5 to E14.5. CXCR4 is activated in NURR1+ cells as they migrate towards the meninges. Accordingly, VM meninges and CXCL12 promoted migration and neuritogenesis of TH+ cells in VM explants in a CXCR4-dependent manner. Moreover, in vivo electroporation of Cxcl12 at E12.5 in the basal plate resulted in lateral migration, whereas expression in the midline resulted in retention of TH+ cells in the IZ close to the midline. Analysis of Cxcr4-/- mice revealed the presence of VM TH+ cells with disoriented processes in the intermediate zone (IZ) at E11.5 and marginal zone (MZ) at E14. Consistently, pharmacological blockade of CXCR4 or genetic deletion of Cxcr4 resulted in an accumulation of TH+ cells in the lateral aspect of the IZ at E14, indicating that CXCR4 is required for the radial migration of mDA neurons in vivo. Altogether, our findings demonstrate that CXCL12/CXCR4 regulates the migration and orientation of processes in A9-A10 mDA neurons.
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