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- Castelo-Branco, GA, et al.
(författare)
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Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a
- 2003
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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. - 0027-8424. ; 100:22, s. 12747-12752
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Tidskriftsartikel (refereegranskat)abstract
- The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that β-catenin is expressed in DA precursor cells and that β-catenin signaling takes place in these cells, as assessed in TOPGAL [Tcf optimal-promoter β-galactosidase] reporter mice. We also found that Wnt-1, -3a, and -5a expression is differentially regulated during development and that partially purified Wnts distinctively regulate VM development. Wnt-3a promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 (Nurr1) but did not increase the number of tyrosine hydroxylase-positive neurons. Instead, Wnt-1 and -5a increased the number of rat midbrain DA neurons in rat embryonic day 14.5 precursor cultures by two distinct mechanisms. Wnt-1 predominantly increased the proliferation of Nurr1+ precursors, up-regulated cyclins D1 and D3, and down-regulated p27 and p57 mRNAs. In contrast, Wnt-5a primarily increased the proportion of Nurr1+ precursors that acquired a neuronal DA phenotype and up-regulated the expression of Ptx3 and c-ret mRNA. Moreover, the soluble cysteine-rich domain of Frizzled-8 (a Wnt inhibitor) blocked endogenous Wnts and the effects of Wnt-1 and -5a on proliferation and the acquisition of a DA phenotype in precursor cultures. These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles.
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| 3. |
- Castelo-Branco, G, et al.
(författare)
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GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons
- 2004
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Ingår i: Journal of cell science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 117:24Pt 24, s. 5731-5737
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Tidskriftsartikel (refereegranskat)abstract
- Wnts are important regulators of dopamine (DA) neuron differentiation in the developing ventral mesencephalon and could thus serve as potential tools in the treatment of Parkinson's disease. In this study, we investigate whether established intracellular Wnt signalling components could modulate the development of DA neurons. Two chemical inhibitors of glycogen synthase kinase (GSK)-3β, indirubin-3-monoxime and kenpaullone, were found to increase neuronal differentiation in ventral mesencephalon precursor cultures. In addition, the GSK-3β-specific inhibitor kenpaullone increased the size of the DA neuron population through conversion of precursors expressing the orphan nuclear receptor-related factor 1 into tyrosine hydroxylase positive neurons, thereby mimicking an effect of Wnts. We show that GSK-3β inhibitors stabilized β-catenin and that overexpression of β-catenin in ventral mesencephalic precursors resulted in increased DA differentiation. The three- to fivefold increase in DA differentiation of precursor cells by GSK-3β inhibitors suggests that such compounds could be used to improve stem/precursor cell therapy approaches in Parkinson's disease.
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| 6. |
- Nilsson, Ulrica, 1960-, et al.
(författare)
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Improved recovery after music and therapeutic suggestions during general anaesthesia : a double-blind randomised controlled trial
- 2001
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 45:7, s. 812-817
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study was designed to determine whether music or music in combination with therapeutic suggestions in the intra-operative period under general anaesthesia could improve the recovery of hysterectomy patients.Methods: In a double-blind randomised clinical investigation, 90 patients who underwent hysterectomy under general anaesthesia were intra-operatively exposed to music, music in combination with therapeutic suggestion or operation room sounds. The anaesthesia was standardised. Postoperative analgesia was provided by a patient-controlled analgesia (PCA). The pain scores were recorded by means of a visual analogue scale. Nausea, emesis, bowel function, fatigue, well-being and duration of hospital stay were studied as outcome variables.Results: On the day of surgery, patients exposed to music in combination with therapeutic suggestions required less rescue analgesic compared with the controls. Patients in the music group experienced more effective analgesia the first day after surgery and could be mobilised earlier after the operation. At discharge from the hospital patients in the music and music combined with therapeutic suggestion group were less fatigued compared to the controls. No differences were noted in nausea, emesis, bowel function, well-being or length of hospital stay between the groups.Conclusion: This double-blind study has demonstrated that intra-operative music and music in combination with therapeutic suggestions may have some beneficial effects on postoperative recovery after hysterectomy. Further controlled studies are necessary to confirm our results.
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