Showing papers by "Anders Björklund published in 2008"

Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.

Abstract: Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.

Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.

Abstract: Appearance of dyskinesia is a common problem of long-term l-DOPA treatment in Parkinson's disease patients and represents a major limitation for the pharmacological management of the motor symptoms in advanced disease stages. We have recently demonstrated that dopamine released from serotonin neurons is responsible for l-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, raising the possibility that blockade of serotonin neuron activity by combination of 5-HT(1A) and 5-HT(1B) agonists could reduce l-DOPA-induced dyskinesia. In the present study, we have investigated the efficacy of 5-HT(1A) and 5-HT(1B) agonists to counteract l-DOPA-induced dyskinesia in 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaques, the gold standard model of Parkinson's disease. In addition, we have studied the ability of this treatment to prevent development of l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. The results demonstrate the existence of a potent synergistic effect between 5-HT(1A) and 5-HT(1B) agonists in their ability to dampen l-DOPA-induced dyskinesia in the MPTP-treated macaques. Sub-threshold doses of the drugs, which individually produced no effect, were able to reduce the abnormal involuntary movements by up to 80% when administered in combination, without affecting the anti-parkinsonian properties of l-DOPA. Furthermore, chronic administration of low doses of the 5-HT(1) agonists in combination was able to prevent development of dyskinesia, and reduce the up-regulation of FosB after daily treatment with l-DOPA in the rat 6-OHDA model. Our results support the importance of a clinical investigation of the effect of 5-HT(1A) and 5-HT(1B) agonists, particularly in combination, in dyskinetic l-DOPA-treated Parkinson's disease patients.

Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion.

Abstract: Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion with haematopoietic cells of the myeloid lineage. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types is induced by organ-specific injuries or whole-body irradiation, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion hybrids, but almost exclusively in response to injuries or inflammation.

Serotonin-dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias.

Abstract: Appearance of dyskinesia is a common problem of long-term Levodopa (L-DOPA) treatment in Parkinson's disease (PD) patients and represents a major limitation for the pharmacological management of the motor symptoms in the advanced stages of disease. An increasing body of evidence points to dopamine released as a false neurotransmitter from the striatal serotonin terminals as the main pre-synaptic determinant of L-DOPA-induced dyskinesia. Here we review the animal experimental and human clinical data in support of this view, which point to the serotonin system as a promising target for anti-dyskinetic therapy in PD patients under L-DOPA medication.

Impact of grafted serotonin and dopamine neurons on development of l-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration

Abstract: Previous studies have shown that serotonin neurons play an important role in the induction and maintenance of l-DOPA-induced dyskinesia in animals with lesion of the nigrostriatal dopamine system. Patients with Parkinson's disease that receive transplants of foetal ventral mesencephalic tissue, the graft cell preparation is likely to contain, in addition to dopamine neurons, serotonin neurons that will vary in number depending on the landmarks used for dissection. Here, we have studied the impact of grafted serotonin neurons—alone or mixed with dopamine neurons—on the development of l-DOPA-induced dyskinesia in rats with a partial 6-hydroxydopamine lesion of the host nigrostriatal projection. In these rats, which showed only low-level dyskinesia at the time of transplantation, serotonin grafts induced a worsening in the severity of dyskinesia that developed during continued l-DOPA treatment, while the dopamine-rich graft had the opposite, dampening effect. The detrimental effect seen in animals with serotonin neuron grafts was dramatically increased when the residual dopamine innervation in the striatum was removed by a second 6-hydroxydopamine lesion. Interestingly, rats with grafts that contained a mixture of dopamine and serotonin neurons (in ∼2:1) showed a marked reduction in l-DOPA-induced dyskinesia over time, and the appearance of severe dyskinesia induced by the removal of the residual dopamine innervation, seen in the animals with transplants of serotonin neurons alone, was blocked. FosB expression in the striatal projection neurons, which is associated with dyskinesias, was also normalized by the dopamine-rich grafts, but not by the serotonin neuron grafts. These data indicate that as long as a sufficient portion, some 10–20%, of the dopamine innervation still remains, the increased host serotonin innervation generated by the grafted serotonin neurons will have limited effect on the development or severity of l-DOPA-induced dyskinesias. At more advanced stages of the disease, when the dopamine innervation of the putamen is reduced below this critical threshold, grafted serotonin neurons are likely to aggravate l-DOPA-induced dyskinesia in those cases where the dopamine re-innervation derived from the grafted neurons is insufficient in magnitude or do not cover the critical dyskinesia-inducing sub-regions of the grafted putamen. We conclude that it is not the absolute number of serotonin neurons in the grafts, but the relative densities of dopamine and serotonin innervations in the grafted striatum that is the critical factor in determining the long-term effect of foetal tissue graft, beneficial or detrimental, on dyskinesia in grafted Parkinson's disease patients.

Intergenerational top income mobility in Sweden: a combination of equal opportunity and capitalistic dynasties

Abstract: This paper presents new evidence on intergenerational income and earnings mobility in the top of the distributions. Using a large dataset of matched father-son pairs in Sweden we are able to obtain results for fractions as small as 0.1 percent of the population. Overall, mobility is lower for incomes than for earnings and it appears to decrease the higher up in the distribution one goes. In the case of incomes, however, we find that mobility decreases dramatically within the top percentile of the population. Our results suggest that Sweden, well-known for its egalitarian achievements, is a society where equality of opportunity for a large majority of wage earners coexists with capitalistic dynasties.

Searching for Optimal Inequality/Incentives

Abstract: This paper examines the evolution of economic inequality in Sweden before, during and after the major macro-economic recession in the early 1990s. Earnings and income inequality increased after the downturn, but government safety net programs buttressed disposable income for those with low income, and despite the rise in inequality, Sweden remained one of the most egalitarian economies in the world. The rise in inequality raised the return to observable skills, but the returns are still too low to explain that Sweden moved to the top of the league tables in knowledge intensive activities. Our analysis of attitudes to inequality shows that more Swedes expressed more concern over the inequity in inequality after the rise in inequality in the 1990s than in the past. Further, more Swedes expressed greater dissatisfaction with wages and working conditions. On the other hand, the rise in unemployment did not reduce overall subjective well being, probably because individuals adapted to higher levels of unemployment.

Searching for Optimal Inequality/Incentives

Abstract: This paper examines the evolution of economic inequality in Sweden before, during and after the major macro-economic recession in the early 1990s. Earnings and income inequality increased after the downturn, but government safety net programs buttressed disposable income for those with low income, and despite the rise in inequality, Sweden remained one of the most egalitarian economies in the world. The rise in inequality raised the return to observable skills, but the returns are still too low to explain that Sweden moved to the top of the league tables in knowledge intensive activities. Our analysis of attitudes to inequality shows that more Swedes expressed more concern over the inequity in inequality after the rise in inequality in the 1990s than in the past. Further, more Swedes expressed greater dissatisfaction with wages and working conditions. On the other hand, the rise in unemployment did not reduce overall subjective well being, probably because individuals adapted to higher levels of unemployment.

Does Marriage Matter for Children? Assessing the Causal Impact of Legal Marriage

Abstract: This paper examines whether parental marriage confers educational advantages to children relative to cohabitation. We exploit a dramatic marriage boom in Sweden in late 1989 created by a reform of the Widow's Pension System that raised the attractiveness of marriage compared to cohabitation to identify the effect of marriage. Sweden's rich administrative data sources enable us to identify the children who were affected by parental marriage due to this marriage boom. Our analysis addresses the policy relevant question whether marginal marriages created by a policy initiative have an impact on children. Using grade point average at age 16 as the outcome variable, we first confirm the expected pattern that children with married parents do better than children with cohabiting parents. However, once we control for observable family background, or use instrumental-variables estimation to compare the outcomes for those children whose parents married due to the reform with those children whose parents remained unmarried, the differences disappeared. A supplementary sibling difference analysis also supports the conclusion that the differentials among children of married and cohabiting parents reflect selection rather than causation.

Intergenerational Top Income Mobility in Sweden: A Combination of Equal Opportunity and Capitalistic Dynasties

Abstract: This paper presents new evidence on intergenerational income and earnings mobility in the top of the distributions. Using a large dataset of matched father-son pairs in Sweden we are able to obtain results for fractions as small as 0.1 percent of the population. Overall, mobil-ity is lower for incomes than for earnings and it appears to decrease the higher up in the distribution one goes. In the case of incomes, however, we find that mobility decreases dramatically within the top percentile of the population. Our results suggest that Sweden, well-known for its egalitarian achievements, is a society where equality of opportunity for a large majority of wage earners coexists with capitalistic dynasties.

Does Marriage Lead to Specialization in Sweden? An Evaluation of Trends in Adult Earnings Before and After Marriage

Abstract: Although a positive male marriage premium has been found in many studies, the source of the premium is unclear and debated – does it result from selection or specialization? Our paper analyzes trends in earnings for married and long-term cohabiting Swedish men, women, and couples who are parents of a random sample of about 130,000 children born in 1977-87. We use panel data on parents’ earnings for six years between 1985 and 1995 to analyze trends in earnings before and after marriage. To identify the effect of marriage on earnings we use the marriage boom in Sweden in 1989, created by the reform of the widow’s pension system and fixed-effects estimation. Our results show that most of the male marriage premium can be explained by positive selection whereas the female marriage penalty seems to reflect both reduced hours of work after marriage, i.e., increased specialization in home production, and other negative effects on earnings of marriage and childcare. The findings suggest that the positive selection of men into marriage translates into the increased specialization of women. We also examine the effect of marriage on total family earnings and find that the net effect of marriage on family earnings is zero because the male marriage premium is offset by the female marriage penalty.

What more than parental income? An exploration of what Swedish siblings get from their parents

Abstract: College choice and subsequent earnings. Results using Swedish sibling data. This paper investigates the relationship between college choice and annual earnings, using within-family variation in college choice. The results show that earnings vary significantly between students who graduated from different types of colleges and the earnings premium is larger for those who graduated at an old university. Do birth order and family size matter for intergenerational income mobility? Evidence from Sweden. Previous studies of intergenerational income mobility have not considered potential birth- order or family-size effects in the estimated income elasticity. This paper estimates the intergenerational income elasticity by birth-order position and family size. The main finding of this paper is that the elasticity tends to decrease with birth order for a given family size, especially for fathers and sons. A comparison of family and neighborhood effects on grades, test scores, educational attainment and income. Evidence from Sweden. This paper compares sibling and neighborhood correlations in school performance, educational attainment and income as a way to learn whether the neighborhood where a child grows up in might explain parts of the sibling similarities found in previous sibling correlation studies. The results show that living in the same neighborhood does not seem to add much to the sibling similarity. What More Than Parental Income? An exploration of what Swedish siblings get from their parents. In this paper, we explore what factors other that parental income can explain why siblings tend to have such similar outcomes as previous correlation studies show. Our results show that parental involvement and attitudes, especially propensity to plan ahead and willingness to postpone benefits to the future, are particularly important for the sibling similarity.

Intergenerational Top Income Mobility in Sweden: A Combination of Equal Opportunity

Abstract: This paper presents new evidence on intergenerational income and earnings mobility in the top of the distributions. Using a large dataset of matched father-son pairs in Sweden we are able to obtain results for fractions as small as 0.1 percent of the population. Overall, mobility is lower for incomes than for earnings and it appears to decrease the higher up in the distribution one goes. In the case of incomes, however, we find that mobility decreases dramatically within the top percentile of the population. Our results suggest that Sweden, well-known for its egalitarian achievements, is a society where equality of opportunity for a large majority of wage earners coexists with capitalistic dynasties.

What More Than Parental Income? An Exploration of What Swedish Siblings Get from Their Parents

Abstract: Sibling correlations are used as overall measures of the impact of family background and community influences on individual outcomes. While most correlation studies show that siblings are quite similar in terms of future achievement, we lack specific knowledge of what it is about family background that really matters. Studies on intergenerational income mobility show that parental income matters to some extent, but they also show that more than half of the family background and community influences that siblings share are not even correlated with parental income. In this paper, we employ a data set that contains rich information about families in order to explore what factors in addition to parental income can explain why siblings tend to have such similar outcomes. Our results show that measures of family structure and social problems account for very little of sibling similarities in adult income above and beyond that already accounted for by parental income. However, when we add a set of indicators for parental involvement and attitudes, the explanatory power of all our variables increased from about a third (using only traditional indicators of socio-economic status) to just over half. Interestingly, indicators of parents' patience, i.e., propensity to plan ahead and willingness to postpone benefits to the future, are particularly important.