Showing papers by "Anders Björklund published in 1994"

Evidence for long‐term survival and function of dopaminergic grafts in progressive Parkinson's disease

Abstract: Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.

Functional neural transplantation

Abstract: In this volume, leading international experts review the present status of all major areas of research in functional neural transplantation. The contributors assess the capacity of neural grafts to repair the structural damage and alleviate the functional consequences of brain damage and neurodegenerative disease. The book begins with detailed coverage of dopamine-rich grafts in parkinsonism, including analyses of the first clinical studies. The authors then review the results of neural grafts in experimental models of cholinergic deficiency, aging, and dementia. Full consideration is given to transplantation strategies used in various neural systems such as the cortex, visual system, hypothalamus, and spinal cord. The final chapter reviews the pharmacological, trophic, and regenerative mechanisms of neural grafts in the brain.

Reversal of spatial memory impairments in aged rats by nerve growth factor and neurotrophins 3 and 4/5 but not by brain-derived neurotrophic factor

Abstract: Aged rats, displaying impairments in spatial learning and memory associated with marked cellular atrophy of forebrain cholinergic neurons, received intracerebroventricular infusions of one of the four neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), or neurotrophin 4/5 (NT-4/5), or a combination of NGF and BDNF, or vehicle. During the 4-week infusion period rats receiving NGF, NT-3, or NT-4/5 showed improved acquisition and retention of spatial memory. With NGF and NT-3, but not NT-4/5, this was accompanied by a significant reduction in cholinergic neuron atrophy in septum, nucleus basalis, and striatum. BDNF, in contrast, was without effect either alone or in combination with NGF. These results show that memory deficits associated with aging can be reversed by several members of the neurotrophin family and that this effect may be mediated through activation of multiple neurotrophin receptors associated with cholinergic and possibly noncholinergic systems in the brain.

Intranigral fetal dopamine grafts induce behavioral compensation in the rat Parkinson model

Abstract: Neural transplantation in experimental Parkinsonism has so far focused on the ectopic placement of fetal ventral mesencephalic (VM) neurons into the dopamine-denervated caudate-putamen. VM grafts are effective in restoring dopamine neurotransmission in the grafted caudate-putamen and in partial amelioration of behavioral deficits. Recent pharmacological and physiological data have provided strong evidence that dopamine released from dendrites of the substantia nigra pars compacta (SNc) neurons within the pars reticulata (SNr) plays an important role in the regulation of the basal ganglia output pathways. Using a novel microtransplantation approach, multiple small cell suspension grafts (250 nl) derived from the VM of E14 rat embryos were implanted into the SNr of unilaterally 6-hydroxydopamine-lesioned rats. Behavioral changes in drug-induced rotation asymmetry were monitored for up to 14 weeks postgrafting, followed by a quantitative assessment and correlation of tyrosine hydroxylase (TH)-positive cell survival. The reduction in rotational asymmetry caused by the intranigral VM grafts was 64% for SKF 38393 (D1 agonist), 54% for apomorphine (mixed D1 and D2 agonist), and 67% for quinpirole (D2 agonist) when compared to a control spinal cord graft group. By contrast, amphetamine-induced rotation was completely unaffected. The correlation between number of TH-positive cells and behavioral compensation was highest for the D1 agonist (R = -0.729), though clear-cut also for the mixed D1/D2 agonist apomorphine (R = -0.664) and the D2 agonist quinpirole (R = -0.642). Favorable morphological features of the VM micrografts included extensive migration of the dopaminergic neurons into the host SNr and the formation of dense patches of dendrite-like TH-positive terminal networks within the SNr. The results demonstrate a novel pattern of behavioral recovery induced by intranigral VM transplants in the rat Parkinson model. This may have important implications for the understanding of how the nigrostriatal dopamine system influences motor control in the basal ganglia as well as for the development of optimal transplantation strategies in Parkinson's disease.

Generating Equality and Eliminating Poverty, the Swedish Way

Abstract: Sweden has a remarkable record in reducing inequality and virtually eliminating poverty. This paper shows that: 1) Sweden achieved its egalitarian income distribution and eliminated poverty largely because of its system of earnings and income determination, not because of the homogeneity of the population nor of its educational system. 2) In the job market Sweden is distinguished by a relatively egalitarian distribution of hours of work among those employed, which may be an interrelated part of the Swedish economic system, and until the recent recession, by a high employment rate. 3) Tax and transfer policies contribute substantially to Sweden's overall distribution record. In contrast to many social welfare systems, Sweden's is largely a workfare system, providing benefits for those with some work activity. 4) Part of Sweden's historic success in maintaining jobs for low wage workers while raising their wages resulted from policies that directly or indirectly buttress demand for low skill workers, notably through public sector employment. 5) Sweden's tax and transfer policies have maintained the position of lower income workers and families, including those with children, during its recent economic decline.

Prefrontal Corticostriatal Afferents Maintain Increased Enkephalin Gene Expression in the Dopamine‐denervated Rat Striatum

Abstract: The cortical contribution to the maintenance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA levels in the rat striatum was investigated using quantitative in situ hybridization histochemistry. The effects of knife-cut transections of the frontal cortical pole on the expression of PPE and PPT mRNA in rat striatal neurons was studied in intact striata and in striata previously denervated by a 6-hydroxydopamine (6-OHDA) lesion of the mesencephalic dopamine pathways. Lesions of the dopaminergic striatal afferents resulted in marked increases in the mRNA encoding PPE throughout the striatum, including the ventral striatum and nucleus accumbens, while the levels of PPT mRNA were considerably reduced in these structures. Knife-cut lesions of the frontal cortical pole, transecting the prefrontal corticostriatal projection at the level of the foreceps minor, displayed little or no effect on the expression of either PPE or PPT mRNA in the dopamine-intact striatum. Conversely, frontal cortical transections performed 4 weeks after the 6-OHDA lesions reversed the 6-OHDA-lesion-induced increase in PPE mRNA in the striatum as well as in the ventral striatum and nucleus accumbens. The down-regulation of PPE mRNA in the dopaminergically denervated striatum was most pronounced in the medial part, which is the area most densely innervated by the frontal cortical pole. Here, the level of PPE mRNA expression per striatal cell was similar to the intact striatum. In contrast, the cellular expression of PPE mRNA remained up-regulated in the lateral striatum, which receives more sparse innervation from the frontal cortical pole. Cortical transections did not significantly affect the 6-OHDA-lesion-induced down-regulation of PPT mRNA in any of the striatal regions analysed. The present results demonstrate that knife-cut transections of the frontal corticostriatal pathway are capable of reversing the increased striatal PPE mRNA levels, but not the decreased PPT mRNA levels, induced by a 6-OHDA lesion of the dopaminergic input. These observations suggest that in the absence of a functional striatal dopamine input, augmented glutamatergic transmission in corticostriatal afferents is necessary to maintain increased levels of PPE mRNA expression, and hence also enkephalin synthesis, in striatal projection neurons.

Brain-derived neurotrophic factor enhances striatal neuropeptide expression in both the intact and the dopamine-depleted rat striatum.

Abstract: In order to elucidate the importance of the striatal GABAergic neurones in mediating functional effects of exogenously applied brain-derived neurotrophic factor (BDNF) in the basal ganglia, we performed daily injections of BDNF or vehicle into the dopamine-depleted striatum of unilaterally 6-hydroxydopamine-lesioned rats for 1 week. In situ hybridization revealed that BDNF exacerbated the lesion-induced up-regulation of preproenkephalin (PPE) mRNA, and completely reversed the lesion-induced decrease of preprotachykinin (PPT) mRNA. In contrast, striatal levels of trkB mRNA were not significantly affected by BDNF administration. Up-regulation of PPE and PPT mRNA was also observed in unlesioned BDNF-injected animals. We conclude that exogenously applied BDNF increases neuropeptide mRNA expression in striatal neurones independently of the presence of a dopaminergic innervation.

Evaluations of Labour Market Policy in Sweden

Abstract: Outlines the current state of evaluation research in Sweden. Concludes that it is limited in scope relative to the USA despite the much larger expenditure on labour market policies in Sweden. Locates this deficiency in the differential research infrastructure of the two countries.

Long distance axonal growth in the adult central nervous system

Abstract: Neuroblasts taken from the developing central nervous system (CNS) can survive and later develop in the lesioned brain of adult recipients. These implanted neuroblasts develop many normal morphological and functional characteristics and, experimentally, substitute for intrinsic neurons. The rat striato-nigral system has been used as a model in which to study the ability of fetal neuroblasts to restore lesioned connections and promote functional recovery in brain lesioned animals. Tissue was obtained from the striatum and substantia nigra region either from E14-15 rat or mouse fetuses, or from 6-8 week old human fetal brain fragments, and implanted into the striatum or substantia nigra of rats previously subjected to neurotoxic lesions at one site or the other. Implanted neurons established extensive and highly specific connections with host cells; and in turn, the striatal implants received connections from all major afferent systems that normally innervate the striatum. In fact, implanted human striatal and nigral neuroblasts showed a remarkable capacity to grow axons along major myelinated pathways and to reach distant target areas.(ABSTRACT TRUNCATED AT 250 WORDS)

The Impact of Family Background on the Returns on and Length of Schooling in Sweden

Abstract: It is a common observation in most societies that children of parents with high incomes, extensive schooling and high-status occupations tend to emulate the behaviour of their parents and in particular invest more in schooling than other children. This pattern is often considered a problem from both equity and efficiency points of views. It represents inequality of opportunity and possibly also inefficiency if the intellectual capacity of all children is not fully exploited. A variety of educational policies have been advocated to reduce the importance of family background for schooling decisions. No country seems, however, to have been very successful in this respect.