Expression of Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 mRNAs in Human Cortical Xenografts

Trophic factors play an important role in the development of neurons and glia. In order to study the involvement of neurotrophins in human cortical development, human fetal parietal cortical tissue, obtained after early elective abortions, was transplanted to cortical cavities in immunosuppressed rats. Using in situ hybridization it was demonstrated that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in developing human cortical xenografts. We conclude that neurotrophins may play a role in human cortical development and rat-derived astroglial cells could be involved in establishing reciprocal “permissive sites”

Оценка буровых растворов применяемых для бурения продуктивных отложений в скважинах Беларуси

The assembly process of a-synuclein toward amyloid fibers is linked to neurodegeneration in Parkinson´s disease. In the present study, we capitalized on the in vitro discovery of a small-molecule accelerator of a-synuclein amyloid formation and assessed its effects when injected in brains of normal mice. An accelerator and an inhibitor of a-synuclein amyloid formation, as well as vehicle only, were injected into the striatum of normal mice and follwed by behavioral evaluation, immunohistochemistry, and metabolomics up to six months later. The effects of molecules injected into the substansia nigra of normal and a-synuclein knockout mice were also analyzed. When accelerator or inhibitor was injected into the brain of normal mice no acute compound toxicity was found. However, 6 months after single striatal injection of accelerator, mice sensorimotor functions were impaired, whereas mice injected with inhibitor had no dysfunctions. Injection of accelerator (but not inhibitor or vehicle) into the substantia nigra revealed singificant loss of tyrosine hydroxylase (TH)-positive neurons after 3 months. No loss of TH-positive neurons was found in a-synuclein knock-out mice injected with accelerator intor the substantia nigra. Metabolic serum profiles from accelerator-injected normal mice matched those of newly diagnosed Parkinson´s disease patients, whereas the profiles from inhibitor-injected normal mice matched controls. Single inoculation of a small-molecule amyloid accelerator may be a new approach for studies of early events during dopamine neurodegeneration in mice

GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function

Peer reviewe

Antioxidant-enriched diet affects early microglia accumulation and promotes regeneration of the striatal dopamine system after a 6-hydroxidopamine-induced lesion in a rat

Neuroinflammation is found both in the brain of humans suffering from Parkinson's disease and in animal models of disease. It is suggested to be involved in the pathogenesisof the disease. In the present study, in order to study the effects of antioxidants on neuroinflammation, microglial phenotypes were evaluated in rats fed with diets containing bilberries, blueberries, or crowberries at 1 and 4 weeks following striatal injection of 6-hydroxydopamine. The dopamine innervation was visualized using antibodies raised againsttyrosine hydroxlase (TH) in the striatum and in the globus pallidus. One week post-lesion, the expression of Iba1-positive cells, a general microglial marker, was significantly increased in the striatum of all animals fed with antioxidant-enriched diets compared to control-diet fed animals, while the diameter of the TH-negative zone was similar in all animals. At four weeks post-lesion, the Iba1-positive microglia was significantly reduced in animals fed with antioxidant-enriched diets. The diameter of the TH-negative zone was significantly reduced in animals fed bilberry and crowberry. The expression and distribution of ED1-positive cells was similar to that of Iba1-positive cells found in the lesionedareas. A cell division marker Ki67 revealed that few microglia were proliferating in crowberry-treated animals. Otherwise dividing cells were associated with blood capillary cells. Although the antioxidant level should be equal in the entire brain, no regeneration was found in globus pallidus, suggesting the mechanism promoting regeneration in the striatum is not effective in the globus pallidus. In conclusion, diets rich in bilberries and crowberries and with high contents of antioxidants stimulate an early phase of accumulation of reactive migroglia that fades at longer time points i.e. promotes regeneration of the striatal dopamine system

Magnetic Resonance Imaging (MRI) to Study Striatal Iron Accumulation in a Rat Model of Parkinson's Disease

Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI). The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron

Striatal Glutamate Release in L-DOPA-Induced Dyskinetic Animals

L-DOPA-induced dyskinesia is a common side effect developed after chronic treatment with 3,4-dihydroxyphenyl-L-alanine (L-DOPA) in Parkinson's disease. The biological mechanisms behind this side effect are not fully comprehended although involvement of dopaminergic, serotonergic, and glutamatergic systems has been suggested. The present study utilizes in vivo amperometry to investigate the impact from unilateral 6-hydroxydopamine lesions and L-DOPA (4 mg/kg, including benserazide 15 mg/kg) -induced dyskinetic behavior on striatal basal extracellular glutamate concentration and potassium-evoked glutamate release in urethane-anesthetized rats. Recordings were performed before and after local L-DOPA application in the striatum. In addition, effects from the 5-HT1A receptor agonist (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OHDPAT; 1 mg/kg) was assessed on glutamate release and on dyskinetic behavior. The results revealed a bilateral similar to 30% reduction of basal extracellular glutamate concentration and attenuated potassium-evoked glutamate release after a unilateral dopamine-depletion in L-DOPA naive animals. In dyskinetic subjects, basal glutamate concentration was comparable to normal controls, although potassium-evoked glutamate release was reduced to similar levels as in drug naive dopamine-lesioned animals. Furthermore, acute striatal L-DOPA administration attenuated glutamate release in all groups, except in the dopamine-lesioned striatum of dyskinetic animals. Co-administration of 8-OHDPAT and L-DOPA decreased dyskinesia in dopamine-lesioned animals, but did not affect potassium-evoked glutamate release, which was seen in normal animals. These findings indicate altered glutamate transmission upon dopamine-depletion and dyskinesia

The birth, rise and success (or fall?) of an intervention project : GodA – a project set up to test a model of the prerequisites for a healthy workplace

Conditions in today’s working life make new approaches necessary in order to limit negative health effects of working life and to enhance wellbeing and health at work. Despite rather progressive legislation, a century of labour inspections, and the efforts of thousands of occupational health personnel, still around 20% of the Swedish workforce report to have had work-related disorders other than accidents during the last year (1). Even if this "elimination approach" partly has succeeded it´s obvious that it is insufficient or inadequate for a working life where key issues for progress are motivation, cooperation and creativity (2). In order to achieve a sustainable working life, not the least to coop with issues related to the ageing population in the developed countries, it is likely that strategies and actions from different and new angles are needed. Healthy workplace has been defined as an organization that maximizes the integration of worker goals for wellbeing and company objectives for profitability and productivity(3). It is noteworthy that the notion healthy workplace is not a substitute for good work environment it is a consequence. Different models, e.g. the PATH-model by Grawitch et al.(4) shows a synthesis of earlier research in a number of different disciplines and frames how a healthy workplace with wellbeing for the individual and organizational improvements can be achieved. Five general categories of healthy workplace practices were identified in the literature: work-life balance, employee growth and development, health and safety, recognition, and employee involvement. Previous research also suggests that the link between these practices and employee and organizational outcomes is contingent on the effectiveness of communication within the organization and the alignment of workplace practices with the organizational context. The GodA-project aims at investigating if work place strategies in line with the PATH-model lead to better health and wellbeing among the employees as well as organizational improvements. The GodA project is a 2 year follow up study with a survey feedback design in three companies with both blue- and white collar workers within the energy sector. One of the companies serves as "intervention company", the other two as controls. The project started out with a pre-project, by means of focus groups and individual interviews, in 2012 in order to find out how employees and managers in the three companies describe the concept of a healthy work environment, what they consider to create well-being at work, and how they perceive their own work environment: What factors are important for well-being at work? presented by T. Karlsson In 2013 a baseline questionnaire where was sent out including items a) based on the results from the pre-study, and b) well-established questions and indices on health and work environment. The results from the survey have been reported back to the companies, which now are processing their results. Research question to be presented and discussed at the symposium: Is there a balance between factors of importance for wellbeing at work and the extent to which they are present at the workplace? presented by P. Lindberg. Is there a correlation between psychosocial work climate indicators and work-related well- The PATH-model emphasizes internal communication as critical in establishing a healthy workplace. As the baseline results show that the communication is not very well developed, this is the primary target for our intervention. We will demonstrate a method for how the survey data are presented back to the intervention company and how they are going to work with the results to improve their work environment, and at the same time enhance communication skills. After our presentation we invite the audience to discuss both the GodA-study and more general methodological issues when conducting intervention-studies, e.g: - When is a company ready (mature) to take part in research activities? - What are the pitfalls in workplace intervention studies? - To what degree can the researchers interact at the workplace and still be objective? - What is the value of focusing on the items that the employees responded to in the survey? References 1. Swedish Work Environment Authority. Work -related disorders 2010 - Arbetsmiljöstatistisk Rapport 2010:4. Stockholm: Swedish Work Environment Authority. & Statistics Sweden 2010. 2. Aronsson G, Gustafsson K, Hakanen J. On the development of a positive work-life psychology. In: Christensen M, editor. Validation and test of central concepts in positive work and organizatinal psychology The second report from the Nordic project 'Positive factors at work'. TemaNord 2009:564. Copenhagen: Nordic Council of Ministers; 2009. p. 93-4. 3. Sauter S, Lim S, Murphy L. Organizational health: A new paradigm for occupational stress research at NIOSH. Japanese Journal of Occupational Mental Health. 1996;4:248-54. 4. Grawitch MJ, Gottschalk M, Munz DC. The path to a healthy workplace: A critical review linking healthy workplace practices, employee well-being, and organizational improvements. Consulting Psychology Journal. 2006;58(3):129-47

2022 års ekonomipris till Ben Bernanke, Douglas Diamond och Philip Dybvig

Kungl. Vetenskapsakademien har beslutat dela ut årets ekonomipris till Ben Bernanke (verksam vid The Brookings Institution), Douglas Diamond (verksam vid University of Chicago) och Philip Dybvig (verksam vid Washington University, St. Louis) ”för forskning om banker och finanskriser”. Med hjälp av forskningsinsikterna från årets ekonomipristagare har senare finanskriser kunnat hanteras bättre

Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia.

l-DOPA is the most commonly used treatment for symptomatic control in patients with Parkinson's disease. Unfortunately, most patients develop severe side-effects, such as dyskinesia, upon chronic l-DOPA treatment. The patophysiology of dyskinesia is unclear; however, involvement of serotonergic nerve fibers in converting l-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of l-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned l-DOPA naïve, and dopamine-denervated chronically l-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local l-DOPA administration into normal and intact hemisphere of dopamine-lesioned l-DOPA naïve animals significantly increased the potassium-evoked dopamine release. l-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted l-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, whereas no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local l-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared with those measured in l-DOPA naïve dopamine-denervated striatum. To conclude, l-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, l-DOPA loading does not increase the dopamine release in dyskinetic animals as found in l-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior