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Dopaminergic neuron

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https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#1
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097465/hydroxysafflor-yellow-a-improves-motor-dysfunction-in-the-rotenone-induced-mice-model-of-parkinson-s-disease
#2
Tian Wang, Lijie Wang, Cuiting Li, Bing Han, Zhenhua Wang, Ji Li, Yan Lv, Shuyun Wang, Fenghua Fu
Dopamine D3 receptor (DRD3) is diminished in patients of Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) is responsible for regulating expression of the DRD3 in the brain. Our previous study showed that hydroxysafflor yellow A (HSYA) could increase BDNF content in the striatum of PD mice. This experiment aimed to evaluate whether HSYA can improve the motor dysfunction induced by rotenone through regulating the BDNF/TrkB/DRD3 signaling pathway in mice. Male C57/BL6 mice were intraperitoneally treated with HSYA...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#3
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096960/estrogen-agonist-genistein-differentially-influences-the-cognitive-and-motor-disorders-in-an-ovariectomized-animal-model-of-parkinsonism
#4
Elaheh Arbabi, Gholamali Hamidi, Sayyed Alireza Talaei, Mahmoud Salami
OBJECTIVES: Parkinson's disease (PD) is a progressive neurological disorder associated with motor disabilities and cognitive dysfunction as well. Evidence indicates that PD occurs less frequently in women than men, confirming a role for steroid hormones in protection of dopaminergic nigrostriatal neurons. It is reported that soy genistein, an estrogen agonist phytoestrogen, display neuroprotective effects against neuronal death. In this study we evaluated the effect of genistein in animal models of Parkinsonism (P) and Parkinsonism + ovariectomized (OP)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#5
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#6
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#7
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28094017/predictive-markers-guide-differentiation-to-improve-graft-outcome-in-clinical-translation-of-hesc-based-therapy-for-parkinson-s-disease
#8
Agnete Kirkeby, Sara Nolbrant, Katarina Tiklova, Andreas Heuer, Nigel Kee, Tiago Cardoso, Daniella Rylander Ottosson, Mariah J Lelos, Pedro Rifes, Stephen B Dunnett, Shane Grealish, Thomas Perlmann, Malin Parmar
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#9
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP(+)-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#10
Federica Bono, Paola Savoia, Adele Guglielmi, Massimo Gennarelli, Giovanna Piovani, Sandra Sigala, Damiana Leo, Stefano Espinoza, Raul R Gainetdinov, Paola Devoto, PierFranco Spano, Cristina Missale, Chiara Fiorentini
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28091566/efficient-generation-of-hpsc-derived-midbrain-dopaminergic-neurons-in-a-fully-defined-scalable-3d-biomaterial-platform
#11
Maroof M Adil, Gonçalo M C Rodrigues, Rishikesh U Kulkarni, Antara T Rao, Nicole E Chernavsky, Evan W Miller, David V Schaffer
Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior)...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089851/neuregulin-1-mutant-mice-indicate-motor-and-sensory-deficits-indeed-few-references-for-schizophrenia-endophenotype-model
#12
Silvia Schneider, Katja Götz, Carmen Birchmeier, Herbert Schwegler, Thomas Roskoden
Neuregulins (Nrg) are a gene family that binds to tyrosine kinase receptors of the ErbB family. The protein of Nrg1 is to be involved in heart formation, migration of neurons, axonal pathfinding and synaptic function. A relation between Nrg1 and schizophrenia is assumed. Chronic impairment in schizophrenia is characterized by different positive and negative symptoms. Detectable markers of this disease in human and in animal models are activity, social behavior and sensory processing. In this study we compared heterozygous Nrg1 mutant mice in behavior and quantification of dopaminergic and serotoninergic neurons with wild type-like littermates...
January 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28089511/the-descending-diencephalic-dopamine-system-is-tuned-to-sensory-stimuli
#13
Sebastian Reinig, Wolfgang Driever, Aristides B Arrenberg
The vertebrate diencephalic A11 system provides the sole dopaminergic innervation of hindbrain and spinal cord and has been implicated in modulation of locomotion and sensory processes. However, the exact contributions of sensory stimuli and motor behavior to A11 dopaminergic activity remain unclear. We recorded cellular calcium activity in four anatomically distinct posterior tubercular A11-type dopaminergic subgroups and two adjacent hypothalamic dopaminergic groups in GCaMP7a-transgenic, semi-restrained zebrafish larvae...
January 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28088342/nanoparticle-standards-for-immuno-based-quantitation-of-%C3%AE-synuclein-oligomers-in-diagnostics-of-parkinson-s-disease-and-other-synucleopathies
#14
Yvonne Herrmann, Tuyen Bujnicki, Christian Zafiu, Andreas Kulawik, Katja Kühbach, Luriano Peters, Judith Fabig, Johannes Willbold, Oliver Bannach, Dieter Willbold
Parkinson's disease is a neurodegenerative disorder that is characterized by symptoms such as rigor, tremor and bradykinesia. A reliable and early diagnosis could improve the development of early therapeutic strategies before death of dopaminergic neurons leads to the first clinical symptoms. The sFIDA (surface-based fluorescence intensity distribution analysis) assay is a highly sensitive method to determine the concentration of α-synuclein (α-syn) oligomers, which are presumably the major toxic isoform of α-syn and potentially the most direct biomarker for PD...
January 11, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28079995/effects-of-cell-cycle-phases-on-the-induction-of-dental-pulp-stem-cells-toward-dopaminergic-like-cells
#15
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Premasangery Kathirvaloo, Sabri Musa, Noor Hayaty Abu Kasim
Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to overcome existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells from deciduous teeth (DPSC) have gained popularity due to their neural crest origin and inherent propensity toward neuronal lineage...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#16
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28077331/physiological-behavioral-changes-induced-by-a-fraction-with-antitumor-cleronade-diterpenes-from-an-atlantic-forest-brazilian-plant-and-computational-intermolecular-interactions-with-neuron-receptors
#17
Éverton José Ferreira de Araújo, Antônia Amanda Cardoso de Almeida, Oskar Almeida Silva, Iwyson Henrique Fernandes da Costa, Luis Mário Rezende Júnior, Francisco das Chagas Alves Lima, Luciano da Silva Lopes, Alberto José Cavalheiro, Paulo Michel Pinheiro Ferreira
ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors...
January 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28076378/p62-pathology-model-in-the-rat-substantia-nigra-with-filamentous-inclusions-and-progressive-neurodegeneration
#18
Kasey L Jackson, Wen-Lang Lin, Sumitra Miriyala, Robert D Dayton, Manikandan Panchatcharam, Kevin J McCarthy, Monica Castanedes-Casey, Dennis W Dickson, Ronald L Klein
One of the proteins most frequently found in neuropathological lesions is the ubiquitin binding protein p62 (sequestosome 1). Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis. Since p62 functions in protein degradation pathways including autophagy, the build-up of p62-positive inclusions suggests defects in protein clearance. p62 was expressed unilaterally in the rat substantia nigra with an adeno-associated virus vector (AAV9) in order to study p62 neuropathology...
2017: PloS One
https://www.readbyqxmd.com/read/28073327/nonmotor-symptoms-in-parkinson-disease
#19
Rosanna Palmeri, Lo Viviana Buono, Francesco Corallo, Maria Foti, Di Giuseppe Lorenzo, Placido Bramanti, Silvia Marino
Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Nonmotor symptoms include cognitive deficits and impairment in emotions recognition ability associated with loss of dopaminergic neurons in the substantia nigra and with alteration in frontostriatal circuits. In this review, we analyzed the studies on social cognition ability in patients with PD. We searched on PubMed and Web of Science databases and screening references of included studied and review articles for additional citations...
January 1, 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28072817/drosophila-clock-is-required-in-brain-pacemaker-neurons-to-prevent-premature-locomotor-aging-independently-of-its-circadian-function
#20
Alexandra Vaccaro, Abdul-Raouf Issa, Laurent Seugnet, Serge Birman, André Klarsfeld
Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock...
January 2017: PLoS Genetics
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