10 results on '"Andrén, Per E."'
Search Results
2. In Vitro Imaging Techniques in Neurodegenerative Diseases
- Author
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Långström, Bengt, Andrén, Per E., Lindhe, Örjan, Svedberg, Marie, and Hall, Håkan
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- 2007
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3. Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy
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Hulme, Heather, Fridjonsdottir, Elva, Gunnarsdottir, Halla, Vallianatou, Theodosia, Zhang, Xiaoqun, Wadensten, Henrik, Shariatgorji, Mohammadreza, Nilsson, Anna, Bezard, Erwan, Svenningsson, Per, Andrén, Per E., Uppsala University, Laboratoire de Mathématiques de Bretagne Atlantique (LMBA), Université de Brest (UBO)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmaceutical Biosciences, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Molecular and Cellular Neuroscience, Rockefeller University [New York], Biomolecular Imaging and Proteomics, National Center for Mass Spectrometry Imaging, Uppsala University, The Rockefeller University, and Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Dyskinesia, Drug-Induced ,Neurologi ,Parkinson's disease ,L-DOPA ,Globus Pallidus ,Dynorphins ,lcsh:RC321-571 ,Levodopa ,Mass spectrometry imaging ,Dynorphin ,[SCCO]Cognitive science ,Parkinsonian Disorders ,Enkephalin ,Animals ,Rats, Wistar ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,ComputingMilieux_MISCELLANEOUS ,musculoskeletal, neural, and ocular physiology ,[SCCO.NEUR]Cognitive science/Neuroscience ,Neurosciences ,Brain ,Enkephalins ,nervous system diseases ,Neostriatum ,Neuropeptide ,Neurology ,nervous system ,Basal ganglia ,Tachykinin ,Neurovetenskaper - Abstract
Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.
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- 2020
4. Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses
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Schintu, Nicoletta, Zhang, Xiaoqun, Stroth, Nikolas, Mathé, Aleksander A., Andrén, Per E., and Svenningsson, Per
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Pharmacology ,Neurologi ,Parkinson's disease ,Neurosciences ,L-DOPA ,tremor ,dyskinesia ,Neurology ,GRASP ,flinders sensitive line ,Parkinson’s disease ,Pharmacology (medical) ,Neurovetenskaper ,Original Research ,tamalin - Abstract
Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1A agonist/D-2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.
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- 2020
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5. Deficits in Motor Performance, Neurotransmitters and Synaptic Plasticity in Elderly and Experimental Parkinsonian Mice Lacking GPR37.
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Zhang, Xiaoqun, Mantas, Ioannis, Fridjonsdottir, Elva, Andrén, Per E., Chergui, Karima, and Svenningsson, Per
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NEUROPLASTICITY ,G protein coupled receptors ,PARKINSON'S disease ,SUBSTANTIA nigra ,GLUTAMATE receptors - Abstract
Parkinson's disease (PD) etiology is attributed to aging and the progressive neurodegeneration of dopamine (DA) neurons of substantia nigra pars compacta (SNc). GPR37 is an orphan G-protein Coupled Receptor (GPCR) that is linked to the juvenile form of PD. In addition, misfolded GPR37 has been found in Lewy bodies. However, properly folded GPR37 found at the cell membrane appears to exert neuroprotection. In the present study we investigated the role of GPR37 in motor deficits due to aging or toxin-induced experimental parkinsonism. Elderly GPR37 knock out (KO) mice displayed hypolocomotion and worse fine movement performance compared to their WT counterparts. Striatal slice electrophysiology reveiled that GPR37 KO mice show profound decrease in long term potentiation (LTP) formation which is accompanied by an alteration in glutamate receptor subunit content. GPR37 KO animals exposed to intrastriatal 6-hydroxydopamine (6-OHDA) show poorer score in the behavioral cylinder test and more loss of the DA transporter (DAT) in striatum. The GPR37 KO striata exhibit a significant increase in GABA which is aggravated after DA depletion. Our data indicate that GPR37 KO mice have DA neuron deficit, enhanced striatal GABA levels and deficient corticostriatal LTP. They also respond stronger to 6-OHDA-induced neurotoxicity. Taken together, the data indicate that properly functional GPR37 may counteract aging processes and parkinsonism. [ABSTRACT FROM AUTHOR]
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- 2020
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6. α-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients.
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Paslawski, Wojciech, Zareba-Paslawska, Justyna, Xiaoqun Zhang, Hölzl, Katharina, Wadensten, Henrik, Shariatgorji, Mohammadreza, Janelidze, Shorena, Hansson, Oskar, Forsgren, Lars, Andrén, Per E., and Svenningsson, Per
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PARKINSON'S disease ,CEREBROSPINAL fluid ,DOPAMINERGIC neurons ,SUBSTANTIA nigra ,MASS spectrometry - Abstract
The progressive accumulation, aggregation, and spread of α-synuclein (αSN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with αSN species, influencing its toxicity in the brain. In the present study, we extended analyses of αSN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that αSN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant αSN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of αSN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for αSN spreading in the extracellular milieu of PD. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology.
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Shariatgorji, Mohammadreza, Svenningsson, Per, and Andrén, Per E
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MASS spectrometry ,NEUROPHARMACOLOGY ,PARKINSON'S disease ,NEUROPSYCHOPHARMACOLOGY ,PROTEINS - Abstract
Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Abnormal structure-specific peptide transmission and processing in a primate model of Parkinson's disease and l-DOPA-induced dyskinesia.
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Bourdenx, Mathieu, Nilsson, Anna, Wadensten, Henrik, Fälth, Maria, Li, Qin, Crossman, Alan R., Andrén, Per E., and Bezard, Erwan
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PARKINSON'S disease , *PEPTIDES , *DOPA , *DYSKINESIAS , *PRIMATES as laboratory animals , *IN situ hybridization , *MASS spectrometry - Abstract
Abstract: A role for enhanced peptidergic transmission, either opioidergic or not, has been proposed for the generation of l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID) on the basis of in situ hybridization studies showing that striatal peptidergic precursor expression consistently correlates with LID severity. Few studies, however, have focused on the actual peptides derived from these precursors. We used mass-spectrometry to study peptide profiles in the putamen and globus pallidus (internalis and externalis) collected from 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine treated macaque monkeys, acutely or chronically treated with l-DOPA. We identified that parkinsonian and dyskinetic states are associated with an abnormal production of proenkephalin-, prodynorphin- and protachykinin-1-derived peptides in both segments of the globus pallidus. Moreover, we report that peptidergic processing is dopamine-state dependent and highly structure-specific, possibly explaining the failure of previous clinical trials attempting to rectify abnormal peptidergic transmission. [Copyright &y& Elsevier]
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- 2014
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9. Caveolin-1 interacts with alpha-synuclein and mediates toxic actions of cellular alpha-synuclein overexpression
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Madeira, Alexandra, Yang, Junfeng, Zhang, Xiaoqun, Vikeved, Elisabet, Nilsson, Anna, Andrén, Per E., and Svenningsson, Per
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PARKINSON'S disease , *CELL death , *NEUROTOXICOLOGY , *PROTEINS , *LIPIDS , *CELL membranes , *NEUROBLASTOMA , *CHEMICAL inhibitors - Abstract
Abstract: Caveolin-1 (Cav-1) is a transmembrane protein which clusters proteins and lipids at the cell membrane into a subclass of lipid rafts named caveolae. To increase our understanding about putative functions of Cav-1 in neuronal cells, we used mouse brain extracts and a novel technology coupling surface plasmon resonance to mass spectrometry to find binding partners to Cav-1. An interaction between Cav-1 and alpha-synclein was found and confirmed in reciprocal pulldown experiments. Genetic overexpression of alpha-synclein in mouse neuroblastoma Neuro2A cells (N2A) expectedly decreased cell survival, but also significantly increased the levels of Cav-1. Furthermore, si-RNA-mediated knockdown of Cav-1 counteracted cell death induced by overexpression of alpha-synuclein. We also used an inhibitor of proteasome (MG132) to induce cell death in a Parkinson’s disease context. Cav-1 knockdown had no effect on cell death induced by MG132. Conversely, treating the cells with mevastatin, an inhibitor of cholesterol synthesis, inhibits cell death induced by MG132, but not by alpha synuclein overexpression. It can be concluded that Cav-1 may play a functional role in neuronal cells by virtue of its physical interaction with alpha-synuclein and regulate alpha synuclein-mediated actions on cell death, processes known to be involved in synucleinopathies including Parkinson’s disease. [Copyright &y& Elsevier]
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- 2011
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10. Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism
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Klintenberg, Rebecka, Arts, Joris, Jongsma, Minke, Wikström, Håkan, Gunne, Lars, and Andrén, Per E.
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DOPAMINE , *PARKINSON'S disease , *PROSENCEPHALON - Abstract
The effects on motor behavior of a new potential dopamine stabilizer: 2-amino-6-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (GMC1111) were investigated in common marmosets with 6-hydroxydopamine lesions within the median forebrain bundle (12 unilateral, 6 bilateral). GMC1111 was administered orally or subcutaneously (s.c.) to unilaterally 6-hydroxydopamine lesioned monkeys, either alone or together with s.c. injections of apomorphine (0.2 mg/kg) and the effect on rotational behavior was examined. GMC1111 (0.03–3.0 mg/kg) alone, orally or s.c., did not induce rotational behavior. When apomorphine and GMC1111 were injected simultaneously, rotations were nearly abolished in three monkeys with a baseline apomorphine-induced rotation rate below 13/min, whereas GMC1111 did not modify the rotations in three high-rotating animals (>17/min). Oral administration of GMC1111 (1.0 and 3.0 mg/kg) abolished the apomorphine-induced rotations in another six unilaterally dopamine-denervated monkeys, indicating a good oral bioavailability. A low dose of GMC1111 (0.3 mg/kg) administered s.c. to marmosets with bilateral nigrostriatal lesions produced a reduction of Parkinson symptoms of approximately the same degree as with levodopa/benserazide (15/3.75 mg/kg), while higher doses of GMC1111 were less effective. When levodopa/benserazide was administered together with various doses of GMC1111 (0.3–3.0 mg/kg), the levodopa-induced peak-dose dyskinesias were reduced with the highest dose of GMC1111 (3 mg/kg). Taken together, GMC1111 modifies dopaminergic activity in a normalizing direction. Parkinson symptoms, as well as levodopa-induced dyskinesias are both reduced. This suggests the arrival of another member of the new dopamine stabilizer family. [Copyright &y& Elsevier]
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- 2003
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