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Anders Björklund

Bio: Anders Björklund is an academic researcher from Lund University. The author has contributed to research in topics: Transplantation & Dopamine. The author has an hindex of 165, co-authored 769 publications receiving 84268 citations. Previous affiliations of Anders Björklund include University of Washington & Institute for the Study of Labor.


Papers
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Book ChapterDOI
TL;DR: This work provides a comprehensive review and critical appraisal of the most commonly used mammalian models of Parkinson's disease, which are produced in rats and mice.
Abstract: Animal models of Parkinson's disease (PD) are essential to investigate pathogenic pathways at the whole-organism level. Moreover, they are necessary for a preclinical investigation of potential new therapies. Different pathological features of PD can be induced in a variety of invertebrate and vertebrate species using toxins, drugs, or genetic perturbations. Each model has a particular utility and range of applicability. Invertebrate PD models are particularly useful for high throughput-screening applications, whereas mammalian models are needed to explore complex motor and non-motor features of the human disease. Here, we provide a comprehensive review and critical appraisal of the most commonly used mammalian models of PD, which are produced in rats and mice. A substantial loss of nigrostriatal dopamine neurons is necessary for the animal to exhibit a hypokinetic motor phenotype responsive to dopaminergic agents, thus resembling clinical PD. This level of dopaminergic neurodegeneration can be induced using specific neurotoxins, environmental toxicants, or proteasome inhibitors. Alternatively, nigrostriatal dopamine degeneration can be induced via overexpression of α-synuclein using viral vectors or transgenic techniques. In addition, protein aggregation pathology can be triggered by inoculating preformed fibrils of α-synuclein in the substantia nigra or the striatum. Thanks to the conceptual and technical progress made in the past few years a vast repertoire of well-characterized animal models are currently available to address different aspects of PD in the laboratory.

23 citations

Journal ArticleDOI
TL;DR: This study provides compelling evidence in favor for the use of immunosuppression in all grafted PD patients receiving cell replacement therapy, regardless of the immunological mismatch between donor and host cells, and suggests that cyclosporine treatment itself may act as a disease-modifying therapy in all PD patients.
Abstract: The early clinical trials using fetal ventral mesencephalic (VM) allografts in Parkinson’s disease (PD) patients have shown efficacy (albeit not in all cases) and have paved the way for further development of cell replacement therapy strategies in PD. The preclinical work that led to these clinical trials used allografts of fetal VM tissue placed into 6-OHDA lesioned rats, while the patients received similar allografts under cover of immunosuppression in an α-synuclein disease state. Thus developing models that more faithfully replicate the clinical scenario would be a useful tool for the translation of such cell-based therapies to the clinic. Here, we show that while providing functional recovery, transplantation of fetal dopamine neurons into the AAV-α-synuclein rat model of PD resulted in smaller-sized grafts as compared to similar grafts placed into the 6-OHDA-lesioned striatum. Additionally, we found that cyclosporin treatment was able to promote the survival of the transplanted cells in this allografted state and surprisingly also provided therapeutic benefit in sham-operated animals. We demonstrated that delayed cyclosporin treatment afforded neurorestoration in three complementary models of PD including the Thy1-α-synuclein transgenic mouse, a novel AAV-α-synuclein mouse model, and the MPTP mouse model. We then explored the mechanisms for this benefit of cyclosporin and found it was mediated by both cell-autonomous mechanisms and non-cell autonomous mechanisms. This study provides compelling evidence in favor for the use of immunosuppression in all grafted PD patients receiving cell replacement therapy, regardless of the immunological mismatch between donor and host cells, and also suggests that cyclosporine treatment itself may act as a disease-modifying therapy in all PD patients.

23 citations

Journal ArticleDOI
TL;DR: In a series of biochemical, fluorescence histochemical, and electron microscopic studies, performed in collaboration with Baumgarten, Lachenmayer, and Schlossberger, it is shown that 5,6-DHT caused profound and fairly selective degeneration of serotonin-containing axons and terminals after intraventricular injection in the rat brain.
Abstract: Inspired by Thoenen and Tranzer's discovery of the selective neurotoxic properties of 6-hydroxydopamine (6-OHDA) on adrenergic neurons,' Baumgarten and Schlossberger synthesized the analogous indoleamine derivative 5,6dihydroxytryptamine (5,6-DHT; see References 2 and 3). In a series of biochemical, fluorescence histochemical, and electron microscopic studies, performed in collaboration with Baumgarten, Lachenmayer, and Schlossberger, we showed that 5,6-DHT caused profound and fairly selective degeneration of serotonin-containing axons and terminals after intraventricular injection in the rat brain:\" The development of neurotoxic drugs with selective or preferential actions on the indoleaminergic systems is, of course, of great interest in functional studies due to the widespread distribution and relatively diffuse organization of these systems. It is obvious that chemical denervation offers possibilities for overcoming the drawbacks inherent in denervation through mechanical or electrolytic lesions of the serotonin systems, which in the brain inevitably involve several different neuronal systems and nonneuronal tissue elements. Furthermore, the serotonin neurotoxins have proved to be highly useful tools in neuroanatomic research, because the axonal lesions induced by these substances in indoleamine axons are much superior to mechanical or electrolytic lesions in producing extensive accumulation of fluorescence in the lesioned axonal pathways; 6 . 8-10 this advantage facilitates greatly the fluorescence histochemical tracing of monoamine-containing fibers. 5,6-Dihydroxytryptamine and other neurotoxic tryptamines were soon applied to a broad field of indoleamine research, and, as reflected, for instance, in this monograph, a vast literature has appeared since 1971 dealing with the serotonin neurotoxins in relation to the morphology and function of serotonin neurons in the central nervous system. This review will summarize the in vitro and in vivo studies performed in our laboratory dealing with the potency of 17 substituted tryptamines in producing toxic damage to serotonergic and catecholaminergic axons in the central nervous system.

22 citations

01 Jan 2010
TL;DR: In this paper, Huvudfragan et al. present a rapport with Vilka arbetsmarknadseffekter har svensk utbildningspolitik.
Abstract: Avsevarda resurser laggs pa utbildning i alla OECD lander. Sverige ar inget undantag: De direkta utbildningsutgifterna utgjorde 6,3 % av BNP 2006, vilket kan jamforas med 5,7 % som genomsnitt i OECD vid samma tidpunkt (OECD 2009). Vilka intakter generar da dessa utgifter? Ett viktigt motiv for utbildningsinsatserna ar att forbattra individers kunskaper vilket i sin tur ska hoja deras produktivitet och forbattra deras sysselsattningsmojligheter, nagot som okar den samlade produktionen i landet. Syftet med denna rapport ar att undersoka om utbildningsinsatser har sadana effekter for den enskilde individen. Huvudfragan i rapporten ar: Vilka arbetsmarknadseffekter har svensk utbildningspolitik? Med ”arbetsmarknadseffekter” menar vi huvudsakligen effekter pa individers loner, sysselsattning och arbetsinkomster. Men vi kommer ocksa att studera utfall som betyg och testresultat.

22 citations

Journal ArticleDOI
TL;DR: Two researchers debate the use of animal models in Parkinson's disease research with Roger Barker taking the view that such models are not useful and may even be misleading, while Anders Björklund defends their use and highlights their value in better understanding and treating this condition.
Abstract: The use of animal models in Parkinson's disease research has been controversial in terms of how well they relate to the clinical condition and thus their utility for translating therapies from the lab to the clinic. In this article, two researchers debate this issue with Roger Barker taking the view that such models are not useful and may even be misleading, while Anders Bjorklund defends their use and highlights their value in better understanding and treating this condition.

22 citations


Cited by
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Book
01 Jan 2001
TL;DR: This is the essential companion to Jeffrey Wooldridge's widely-used graduate text Econometric Analysis of Cross Section and Panel Data (MIT Press, 2001).
Abstract: The second edition of this acclaimed graduate text provides a unified treatment of two methods used in contemporary econometric research, cross section and data panel methods. By focusing on assumptions that can be given behavioral content, the book maintains an appropriate level of rigor while emphasizing intuitive thinking. The analysis covers both linear and nonlinear models, including models with dynamics and/or individual heterogeneity. In addition to general estimation frameworks (particular methods of moments and maximum likelihood), specific linear and nonlinear methods are covered in detail, including probit and logit models and their multivariate, Tobit models, models for count data, censored and missing data schemes, causal (or treatment) effects, and duration analysis. Econometric Analysis of Cross Section and Panel Data was the first graduate econometrics text to focus on microeconomic data structures, allowing assumptions to be separated into population and sampling assumptions. This second edition has been substantially updated and revised. Improvements include a broader class of models for missing data problems; more detailed treatment of cluster problems, an important topic for empirical researchers; expanded discussion of "generalized instrumental variables" (GIV) estimation; new coverage (based on the author's own recent research) of inverse probability weighting; a more complete framework for estimating treatment effects with panel data, and a firmly established link between econometric approaches to nonlinear panel data and the "generalized estimating equation" literature popular in statistics and other fields. New attention is given to explaining when particular econometric methods can be applied; the goal is not only to tell readers what does work, but why certain "obvious" procedures do not. The numerous included exercises, both theoretical and computer-based, allow the reader to extend methods covered in the text and discover new insights.

28,298 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Book
28 Apr 2021
TL;DR: In this article, the authors proposed a two-way error component regression model for estimating the likelihood of a particular item in a set of data points in a single-dimensional graph.
Abstract: Preface.1. Introduction.1.1 Panel Data: Some Examples.1.2 Why Should We Use Panel Data? Their Benefits and Limitations.Note.2. The One-way Error Component Regression Model.2.1 Introduction.2.2 The Fixed Effects Model.2.3 The Random Effects Model.2.4 Maximum Likelihood Estimation.2.5 Prediction.2.6 Examples.2.7 Selected Applications.2.8 Computational Note.Notes.Problems.3. The Two-way Error Component Regression Model.3.1 Introduction.3.2 The Fixed Effects Model.3.3 The Random Effects Model.3.4 Maximum Likelihood Estimation.3.5 Prediction.3.6 Examples.3.7 Selected Applications.Notes.Problems.4. Test of Hypotheses with Panel Data.4.1 Tests for Poolability of the Data.4.2 Tests for Individual and Time Effects.4.3 Hausman's Specification Test.4.4 Further Reading.Notes.Problems.5. Heteroskedasticity and Serial Correlation in the Error Component Model.5.1 Heteroskedasticity.5.2 Serial Correlation.Notes.Problems.6. Seemingly Unrelated Regressions with Error Components.6.1 The One-way Model.6.2 The Two-way Model.6.3 Applications and Extensions.Problems.7. Simultaneous Equations with Error Components.7.1 Single Equation Estimation.7.2 Empirical Example: Crime in North Carolina.7.3 System Estimation.7.4 The Hausman and Taylor Estimator.7.5 Empirical Example: Earnings Equation Using PSID Data.7.6 Extensions.Notes.Problems.8. Dynamic Panel Data Models.8.1 Introduction.8.2 The Arellano and Bond Estimator.8.3 The Arellano and Bover Estimator.8.4 The Ahn and Schmidt Moment Conditions.8.5 The Blundell and Bond System GMM Estimator.8.6 The Keane and Runkle Estimator.8.7 Further Developments.8.8 Empirical Example: Dynamic Demand for Cigarettes.8.9 Further Reading.Notes.Problems.9. Unbalanced Panel Data Models.9.1 Introduction.9.2 The Unbalanced One-way Error Component Model.9.3 Empirical Example: Hedonic Housing.9.4 The Unbalanced Two-way Error Component Model.9.5 Testing for Individual and Time Effects Using Unbalanced Panel Data.9.6 The Unbalanced Nested Error Component Model.Notes.Problems.10. Special Topics.10.1 Measurement Error and Panel Data.10.2 Rotating Panels.10.3 Pseudo-panels.10.4 Alternative Methods of Pooling Time Series of Cross-section Data.10.5 Spatial Panels.10.6 Short-run vs Long-run Estimates in Pooled Models.10.7 Heterogeneous Panels.Notes.Problems.11. Limited Dependent Variables and Panel Data.11.1 Fixed and Random Logit and Probit Models.11.2 Simulation Estimation of Limited Dependent Variable Models with Panel Data.11.3 Dynamic Panel Data Limited Dependent Variable Models.11.4 Selection Bias in Panel Data.11.5 Censored and Truncated Panel Data Models.11.6 Empirical Applications.11.7 Empirical Example: Nurses' Labor Supply.11.8 Further Reading.Notes.Problems.12. Nonstationary Panels.12.1 Introduction.12.2 Panel Unit Roots Tests Assuming Cross-sectional Independence.12.3 Panel Unit Roots Tests Allowing for Cross-sectional Dependence.12.4 Spurious Regression in Panel Data.12.5 Panel Cointegration Tests.12.6 Estimation and Inference in Panel Cointegration Models.12.7 Empirical Example: Purchasing Power Parity.12.8 Further Reading.Notes.Problems.References.Index.

10,363 citations

Journal ArticleDOI
11 Sep 2003-Neuron
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.

4,872 citations