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Parkinson's disease animal models

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https://www.readbyqxmd.com/read/28716706/characterization-of-a-presymptomatic-stage-in-a-drosophila-parkinson-s-disease-model-unveiling-dopaminergic-compensatory-mechanisms
#1
Daniela Molina-Mateo, Nicolás Fuenzalida-Uribe, Sergio Hidalgo, Claudia Molina-Fernández, Jorge Abarca, Rafaella V Zárate, Marcela Escandón, Reinaldo Figueroa, María Florencia Tevy, Jorge M Campusano
Parkinson disease (PD) is a degenerative disorder characterized by several motor symptoms including shaking, rigidity, slow movement and difficult walking, which has been associated to the death of nigro-striatal dopaminergic neurons. >90% of PD patients also present olfactory dysfunction. Although the molecular mechanisms responsible for this disease are not clear, hereditary PD is linked to mutations in specific genes, including the PTEN-induced putative kinase 1 (PINK1). In this work we provide for the first time a thorough temporal description of the behavioral effects induced by a mutation in the PINK1 gene in adult Drosophila, a previously described animal model for PD...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28711409/nortriptyline-inhibits-aggregation-and-neurotoxicity-of-alpha-synuclein-by-enhancing-reconfiguration-of-the-monomeric-form
#2
Timothy J Collier, Kinshuk R Srivastava, Craig Justman, Tom Grammatopoulous, Birgit Hutter-Paier, Manuela Prokesch, Daniel Havas, Jean-Christophe Rochet, Fang Liu, Kevin Jock, Patrícia de Oliveira, Georgia L Stirtz, Ulf Dettmer, Caryl E Sortwell, Mel B Feany, Peter Lansbury, Lisa Lapidus, Katrina L Paumier
The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28702721/peptides-semax-and-selank-affect-the-behavior-of-rats-with-6-ohda-induced-pd-like-parkinsonism
#3
P A Slominsky, M I Shadrina, T A Kolomin, A V Stavrovskaya, E V Filatova, L A Andreeva, S N Illarioshkin, N F Myasoedov
Parkinson's disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals...
May 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28701928/the-hyperpolarization-activated-current-determines-synaptic-excitability-calcium-activity-and-specific-viability-of-substantia-nigra-dopaminergic-neurons
#4
Carmen Carbone, Alessia Costa, Gustavo Provensi, Guido Mannaioni, Alessio Masi
Differential vulnerability between Substantia Nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of Parkinson's disease (PD). Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28701075/the-effect-of-orexin-a-on-motor-and-cognitive-functions-in-a-rat-model-of-parkinson-s-disease
#5
Zahra Hadadianpour, Farangis Fatehi, Fateme Ayoobi, Ayat Kaeidi, Ali Shamsizadeh, Iman Fatemi
OBJECTIVE:  The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson's disease. METHODS: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests...
July 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28698835/historical-perspective-of-cell-transplantation-in-parkinson-s-disease
#6
REVIEW
Alejandra Boronat-García, Magdalena Guerra-Crespo, René Drucker-Colín
Cell grafting has been considered a therapeutic approach for Parkinson's disease (PD) since the 1980s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of cell-transplantation for PD consists in grafting dopamine-producing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients...
June 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28695985/intrastriatal-administration-of-botulinum-neurotoxin-a-normalizes-striatal-d2-r-binding-and-reduces-striatal-d1-r-binding-in-male-hemiparkinsonian-rats
#7
Franziska Wedekind, Angela Oskamp, Markus Lang, Alexander Hawlitschka, Karl Zilles, Andreas Wree, Andreas Bauer
Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7)...
July 11, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28680396/botulinum-neurotoxin-a-injected-ipsilaterally-or-contralaterally-into-the-striatum-in-the-rat-6-ohda-model-of-unilateral-parkinson-s-disease-differently-affects-behavior
#8
Veronica A Antipova, Carsten Holzmann, Oliver Schmitt, Andreas Wree, Alexander Hawlitschka
Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28677758/transcriptome-profiling-of-the-subventricular-zone-and-dentate-gyrus-in-an-animal-model-of-parkinson-s-disease
#9
Xin-Jie Bao, Geng-Chao Wang, Fu-Xing Zuo, Xue-Yuan Li, Jun Wu, Guo Chen, Wan-Chen Dou, Yi Guo, Qin Shen, Ren-Zhi Wang
Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28673834/enzymatic-o-glcnacylation-of-%C3%AE-synuclein-reduces-aggregation-and-increases-sds-resistant-soluble-oligomers
#10
Jiaming Zhang, Haozhi Lei, Yubei Chen, Yan-Tao Ma, Fang Jiang, Jieqiong Tan, Yi Zhang, Jia-Da Li
Neurodegenerative diseases including dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, and Parkinson's disease are associated with the aberrant aggregation of α-synuclein, which is influenced by several post-translational modifications (PTMs). O-GlcNAcylation is one PTM that has an important role in many fundamental processes. The O-GlcNAcylation of endogenous α-synuclein at residues 53, 64, 72 and 87 has been reported in an unbiased mass spectrum analysis. The consequences of O-GlcNAcylation at residues 72 or 87 have been studied by using a synthetic α-synuclein bearing O-GlcNAcylation at threonine residue 72 or serine 87, respectively...
July 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28673739/sirtuin-3-rescues-neurons-through-the-stabilisation-of-mitochondrial-biogenetics-in-the-virally-expressing-mutant-%C3%AE-synuclein-rat-model-of-parkinsonism
#11
Jacqueline A Gleave, Lindsay R Arathoon, Dennison Trinh, Kristin E Lizal, Nicolas Giguère, James H M Barber, Zainab Najarali, M Hassan Khan, Sherri L Thiele, Mahin S Semmen, James B Koprich, Jonathan M Brotchie, James H Eubanks, Louis-Eric Trudeau, Joanne E Nash
Parkinson's disease (PD) is a neurodegenerative movement disorder, which affects approximately 1-2% of the population over 60years of age. Current treatments for PD are symptomatic, and the pathology of the disease continues to progresses over time until palliative care is required. Mitochondria are key players in the pathology of PD. Genetic and post mortem studies have shown a large number of mitochondrial abnormalities in the substantia nigra pars compacta (SNc) of the parkinsonian brain. Furthermore, physiologically, mitochondria of nigral neurons are constantly under unusually high levels of metabolic stress because of the excitatory properties and architecture of these neurons...
July 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28673122/rejuvenating-effect-of-long-term-igf-i-gene-therapy-in-the-hypothalamus-of-aged-rats-with-dopaminergic-dysfunction
#12
Jose Ignacio Schwerdt, Micaela Lopez-Leon, Gloria Miriam Console, Oscar Alfedo Brown, Gustavo Ramon Morel, Eduardo Spinedi, Rodolfo Gustavo Goya
The aging female rat constitutes an interesting model of spontaneous and progressive age-related dopaminergic dysfunction as it allows assessing new therapeutic strategies for Parkinson's disease. Insulin-like growth factor I (IGF-I) is emerging as a powerful neuroprotective molecule which is strongly induced in the central nervous system after different insults. We constructed a helper-dependent recombinant adenoviral vector (HDRAd-IGFI) harboring the gene for rat IGF-I. This was used it to implement long-term IGF-I gene therapy in the hypothalamus of aged female rats, which display hypothalamic dopaminergic (DA) dysfunction and as a consequence, chronic hyperprolactinemia...
July 3, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28671142/the-role-of-lipids-interacting-with-%C3%AE-synuclein-in-the-pathogenesis-of-parkinson-s-disease
#13
Céline Galvagnion
α-synuclein is a small protein abundantly expressed in the brain and mainly located in synaptic terminals. The conversion of α-synuclein into oligomers and fibrils is the hallmark of a range of neurodegenerative disorders including Parkinson's disease and dementia with Lewy bodies. α-synuclein is disordered in solution but can adopt an α-helical conformation upon binding to lipid membranes. This lipid-protein interaction plays an important role in its proposed biological function, i.e., synaptic plasticity, but can also entail the aggregation of the protein...
June 30, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28659967/behavioral-phenotyping-and-pathological-indicators-of-parkinson-s-disease-in-c-elegans-models
#14
REVIEW
Malabika Maulik, Swarup Mitra, Abel Bult-Ito, Barbara E Taylor, Elena M Vayndorf
Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of α-synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function. The etiology of PD can be attributed to a combination of environmental and genetic factors. A popular animal model, the nematode roundworm Caenorhabditis elegans, has been frequently used to study the role of genetic and environmental factors in the molecular pathology and behavioral phenotypes associated with PD...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28659169/the-novel-compound-pbt434-prevents-iron-mediated-neurodegeneration-and-alpha-synuclein-toxicity-in-multiple-models-of-parkinson-s-disease
#15
David I Finkelstein, Jessica L Billings, Paul A Adlard, Scott Ayton, Amelia Sedjahtera, Colin L Masters, Simon Wilkins, David M Shackleford, Susan A Charman, Wojciech Bal, Izabela A Zawisza, Ewa Kurowska, Andrew L Gundlach, Sheri Ma, Ashley I Bush, Dominic J Hare, Philip A Doble, Simon Crawford, Elisabeth Cl Gautier, Jack Parsons, Penny Huggins, Kevin J Barnham, Robert A Cherny
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions...
June 28, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28655689/assessment-of-gait-dynamics-in-rotenone-induced-rat-model-of-parkinson-s-disease-by-footprint-method
#16
Syeda Madiha, Saiqa Tabassum, Zehra Batool, Laraib Liaquat, Sadia Sadir, Sidrah Shahzad, Tahira Perveen, Saida Haider
Rotenone (organic pesticide and inhibitor of mitochondrial complex I) is used to generate an experimental model of Parkinson's disease (PD). In the present study, we investigated rotenone-induced locomotor deficits, gait dynamics and muscular weakness in rats. The study also determined dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels following rotenone administration. In the study, adult male rats were administered subcutaneously (s.c.) with rotenone (1.5 mg/kg/day) for 8 days. Motor activities were monitored by the Kondziela's inverted screen test, beam walking test and footprint test...
May 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28650954/prevalence-of-sexual-dimorphism-in-mammalian-phenotypic-traits
#17
Natasha A Karp, Jeremy Mason, Arthur L Beaudet, Yoav Benjamini, Lynette Bower, Robert E Braun, Steve D M Brown, Elissa J Chesler, Mary E Dickinson, Ann M Flenniken, Helmut Fuchs, Martin Hrabe de Angelis, Xiang Gao, Shiying Guo, Simon Greenaway, Ruth Heller, Yann Herault, Monica J Justice, Natalja Kurbatova, Christopher J Lelliott, K C Kent Lloyd, Ann-Marie Mallon, Judith E Mank, Hiroshi Masuya, Colin McKerlie, Terrence F Meehan, Richard F Mott, Stephen A Murray, Helen Parkinson, Ramiro Ramirez-Solis, Luis Santos, John R Seavitt, Damian Smedley, Tania Sorg, Anneliese O Speak, Karen P Steel, Karen L Svenson, Shigeharu Wakana, David West, Sara Wells, Henrik Westerberg, Shay Yaacoby, Jacqueline K White
The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649618/synergistic-effects-of-influenza-and-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-can-be-eliminated-by-the-use-of-influenza-therapeutics-experimental-evidence-for-the-multi-hit-hypothesis
#18
Shankar Sadasivan, Bridgett Sharp, Stacey Schultz-Cherry, Richard Jay Smeyne
Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson's disease (Ransohoff, Science 353: 777-783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493-514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131-158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) Movement Disorders: Genetics and Models: 287-306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649132/reassessment-of-subacute-mptp-treated-mice-as-animal-model-of-parkinson-s-disease
#19
Qiu-Shuang Zhang, Yang Heng, Zheng Mou, Ju-Yang Huang, Yu-He Yuan, Nai-Hong Chen
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model remains the most commonly used animal model of Parkinson's disease (PD). There are three MPTP-treatment schemes: acute, subacute and chronic. Considering the advantages of the period and similarity to PD, the subacute model was often chosen to assess the validity of new candidates, but the changes caused by the subacute MPTP treatment and the appropriate positive control for this model remain to be further confirmed. The aim of this study was: 1 to estimate the value of the subacute MPTP mouse model in aspects of behavioral performance, biochemical changes and pathological abnormalities, and 2 to find effective positive drugs...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28645308/neonatal-aav-delivery-of-alpha-synuclein-induces-pathology-in-the-adult-mouse-brain
#20
Marion Delenclos, Ayman H Faroqi, Mei Yue, Aishe Kurti, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, John D Fryer, Pamela J McLean
Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases...
June 23, 2017: Acta Neuropathologica Communications
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