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- Apyan, A., et al.
(author)
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Coherent bremsstrahlung, coherent pair production, birefringence, and polarimetry in the 20-170 GeV energy range using aligned crystals
- 2008
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In: Physical Review Special Topics - Accelerators and Beams. - 1098-4402. ; 11:4, s. 041001-
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Journal article (peer-reviewed)abstract
- The processes of coherent bremsstrahlung (CB) and coherent pair production (CPP) based on aligned crystal targets have been studied in the energy range 20-170 GeV. The experimental arrangement allowed for measurements of single photon properties of these phenomena including their polarization dependences. This is significant as the theoretical description of CB and CPP is an area of active debate and development. With the approach used in this paper, both the measured cross sections and polarization observables are predicted very well. This indicates a proper understanding of CB and CPP up to energies of 170 GeV. Birefringence in CPP on aligned crystals is applied to determine the polarization parameters in our measurements. New technologies for high-energy photon beam optics including phase plates and polarimeters for linear and circular polarization are demonstrated in this experiment. Coherent bremsstrahlung for the strings-on-strings (SOS) orientation yields a larger enhancement for hard photons than CB for the channeling orientations of the crystal. Our measurements and our calculations indicate low photon polarizations for the high-energy SOS photons.
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- Lindgren, Hanna S., et al.
(author)
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Putaminal Upregulation of FosB/ΔFosB-Like Immunoreactivity in Parkinson's Disease Patients with Dyskinesia
- 2011
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:4, s. 347-357
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Journal article (peer-reviewed)abstract
- The transcription factor FosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson´s disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and FosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/ FosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/ FosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/ FosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/ FosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of FosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.
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- Ohlin, Elisabet, et al.
(author)
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Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.
- 2011
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In: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 134, s. 2339-2357
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Journal article (peer-reviewed)abstract
- Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease.
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- Brehm, Nadine, et al.
(author)
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A Genetic Mouse Model of Parkinson’s Disease Shows Involuntary Movements and Increased Postsynaptic Sensitivity to Apomorphine
- 2015
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In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 52:3, s. 1152-1164
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Journal article (peer-reviewed)abstract
- Alpha-synuclein (SNCA) protein aggregation plays a causal role in Parkinson's disease (PD). The SNCA protein modulates neurotransmission via the SNAP receptor (SNARE) complex assembly and presynaptic vesicle trafficking. The striatal presynaptic dopamine deficit is alleviated by treatment with levodopa (L-DOPA), but postsynaptic plastic changes induced by this treatment lead to a development of involuntary movements (dyskinesia). While this process is currently modeled in rodents harboring neurotoxin-induced lesions of the nigrostriatal pathway, we have here explored the postsynaptic supersensitivity of dopamine receptor-mediated signaling in a genetic mouse model of early PD. To this end, we used mice with prion promoter-driven overexpression of A53T-SNCA in the nigrostriatal and corticostriatal projections. At a symptomatic age (18 months), mice were challenged with apomorphine (5 mg/kg s.c.) and examined using both behavioral and molecular assays. After the administration of apomorphine, A53T-transgenic mice showed more severe stereotypic and dystonic movements in comparison with wild-type controls. Molecular markers of extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and dephosphorylation, and Fos messenger RNA (mRNA), were examined in striatal tissue at 30 and 100 min after apomorphine injection. At 30 min, wild-type and transgenic mice showed a similar induction of phosphorylated ERK1/2, Dusp1, and Dusp6 mRNA (two MAPK phosphatases). At the same time point, Fos mRNA was induced more strongly in mutant mice than in wild-type controls. At 100 min after apomorphine treatment, the induction of both Fos, Dusp1, and Dusp6 mRNA was significantly larger in mutant mice than wild-type controls. At this time point, apomorphine caused a reduction in phospho-ERK1/2 levels specifically in the transgenic mice. Our results document for the first time a disturbance of ERK1/2 signaling regulation associated with apomorphine-induced involuntary movements in a genetic mouse model of synucleinopathy. This mouse model will be useful to identify novel therapeutic targets that can counteract abnormal dopamine-dependent striatal plasticity during both prodromal and manifest stages of PD.
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