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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/29163149/gyy4137-an-h2s-slow-releasing-donor-prevents-nitrative-stress-and-%C3%AE-synuclein-nitration-in-an-mptp-mouse-model-of-parkinson-s-disease
#1
Xiaoou Hou, Yuqing Yuan, Yulan Sheng, Baoshi Yuan, Yali Wang, Jiyue Zheng, Chun-Feng Liu, Xiaohu Zhang, Li-Fang Hu
The neuromodulator hydrogen sulfide (H2S) was shown to exert neuroprotection in different models of Parkinson's disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H2S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163030/tcf12-is-involved-in-early-cell-fate-determination-and-subset-specification-of-midbrain-dopamine-neurons
#2
Simone Mesman, Marten P Smidt
The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29152652/effect-of-wnt1-and-wnt5a-on-the-development-of-dopaminergic-neurons-and-toxicity-induced-by-combined-exposure-to-paraquat-and-maneb-during-gestation-and-lactation
#3
Jing Ma, Cui Huang, Kun Ma, Yan-Ping Wu, Bai-Xiang Li, Yan Sun
Paraquat (PQ) and maneb (MB) are widely used herbicides. Wingless (Wnt) proteins serve a role in the development and differentiation of dopaminergic neurons. Previous studies demonstrated that combined exposure to PQ and MB damages dopaminergic neurons in the midbrain. Effects of PQ and MB exposure on midbrain Wnt proteins have also been previously reported. In the present study, from the 5th day of gestation to weaning of the offspring, pregnant Sprague‑Dawley rats were administrated saline, or PQ and MB at two different doses: high, 15 mg/kg body weight PQ + 45 mg/kg body weight MB; or low, 10 mg/kg body weight PQ + 30 mg/kg body weight MB...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29142291/resveratrol-modulates-cocaine-induced-inhibitory-synaptic-plasticity-in-vta-dopamine-neurons-by-inhibiting-phosphodiesterases-pdes
#4
Yan Li, Laikang Yu, Li Zhao, Fanxing Zeng, Qing-Song Liu
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133394/role-of-estrogen-receptor-beta-in-neural-differentiation-of-mouse-embryonic-stem-cells
#5
Mukesh K Varshney, José Inzunza, Diana Lupu, Vaidheeswaran Ganapathy, Per Antonson, Joëlle Rüegg, Ivan Nalvarte, Jan-Åke Gustafsson
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29101619/impairment-of-non-associative-learning-in-a-rat-experimental-model-of-preclinical-stage-of-parkinson-s-disease
#6
I N Abdurasulova, I V Ekimova, A V Matsulevich, A R Gazizova, V M Klimenko, Yu F Pastukhov
An experimental model of the preclinical stage of Parkinson's disease was induced by double intranasal administration of the proteasome inhibitor lactacystin. The results demonstrated signs of cognitive impairments expressed as impaired non-associative learning. This was related to degeneration of one-third of dopaminergic neurons in the ventral tegmental area of the midbrain and their axons in the dorsolateral prefrontal cortex. Impairment of non-associative learning may be an early non-motor marker of Parkinson's disease indicating the start of neurodegenerative processes in the dopaminergic mesocortical system of the brain...
September 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/29064551/organisation-of-the-dopamine-neuronal-subsets-within-midbrain-of-the-pygmy-acrobat
#7
R Krawczyk, I Klejbor, K Turlejski, B Ludkiewicz, J Moryś
Pygmy Acrobat has unique set of morphological, anatomical and behavioral features that make it a promising model for study of primate evolution. Among the many locomotor adaptations, it should be mark a wide range of movements such as gliding, climbing, running, arboreality. This type of behavior can result from differences in anatomy and physiology of the brain systems involved in its integration. It is well acknowledged that dopaminergic neurons are involved in motor control, motivation and cognition. Due to the fact that there are no data on morphological organisation of dopaminergic system in the midbrain of Acrobates pygmaeus, we decide to do this using immunohistochemical and quantitative methods...
October 24, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/29054882/parkinson-s-disease-associated-lrrk2-hyperactive-kinase-mutant-disrupts-synaptic-vesicle-trafficking-in-ventral-midbrain-neurons
#8
Ping-Yue Pan, Xianting Li, Jing Wang, James Powell, Qian Wang, Yuanxi Zhang, Zhaoyu Chen, Bridget Wicinski, Patrick Hof, Timothy A Ryan, Zhenyu Yue
Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear. Here we show that the most common PD mutation LRRK2 G2019S impairs SV endocytosis in ventral midbrain (MB) neurons including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29040870/parkin-absence-accelerates-microtubule-aging-in-dopaminergic-neurons
#9
Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29039078/the-neuroprotective-effects-of-hydro-alcoholic-extract-of-olive-olea-europaea-l-leaf-on-rotenone-induced-parkinson-s-disease-in-rat
#10
Maryam Sarbishegi, Enam Alhagh Charkhat Gorgich, Ozra Khajavi, Gholamreza Komeili, Saeedeh Salimi
Parkinson's disease (PD) is an age-related disease in which dopaminergic neurons in the nigrostriatal pathway are destroyed, resulting in movement and behavioral problems. Oxidative stress and the generation of reactive oxygen species play key roles in neurodegenerative diseases, such as PD. Rotenone (ROT) is a common pesticide that induces oxidative stress. Olive leaves extract (OLE) has antioxidant and neuroprotective effects. Thus, the aim of this study was to investigate the neuroprotective effects of OLE on ROT-induced oxidative stress in the midbrain of a rat model of PD...
October 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29038581/transcriptional-repression-of-plxnc1-by-lmx1a-and-lmx1b-directs-topographic-dopaminergic-circuit-formation
#11
Audrey Chabrat, Guillaume Brisson, Hélène Doucet-Beaupré, Charleen Salesse, Marcos Schaan Profes, Axelle Dovonou, Cléophace Akitegetse, Julien Charest, Suzanne Lemstra, Daniel Côté, R Jeroen Pasterkamp, Monica I Abrudan, Emmanouil Metzakopian, Siew-Lan Ang, Martin Lévesque
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29019159/alpha-lipoamide-ameliorates-motor-deficits-and-mitochondrial-dynamics-in-the-parkinson-s-disease-model-induced-by-6-hydroxydopamine
#12
Bo Zhou, Min Wen, Xin Lin, Yun-Hua Chen, Yun Gou, Yong Li, Yi Zhang, Hong-Wei Li, Lei Tang
The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are not yet fully elucidated; however, evidence from the in vitro and in vivo PD models suggest that mitochondrial dysfunction may play a major role in PD pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is a better cofactor for mitochondrial dehydrogenase with a stronger protective effect on mitochondria than lipoic acid. Identification of these protective effects of alpha lipoamide on mitochondria, together with the evidence that mitochondrial dysfunction plays a critical role in PD, we speculate that alpha lipoamide may exert a protective effect in PD by regulating the mitochondrial function...
October 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28965325/location-and-number-of-astrocytes-determine-dopaminergic-neuron-survival-and-function-under-6-ohda-stress-mediated-through-differential-bdnf-release
#13
Indrani Datta, Kavina Ganapathy, Rema Razdan, Ramesh Bhonde
While astrocytes throughout the CNS share many common traits, they exhibit significant differences in function and number among brain regions. The aim of the present study is to assess the effect of region-specificity and number of astrocytes on the survival of dopaminergic neurons under stress, and to understand the possible mechanism by which these astrocytes extend neuroprotection to dopaminergic neurons. Purified astrocytes obtained from forebrain, midbrain, and hindbrain region were characterized through FACS and immunofluorescence...
September 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28958789/expression-analyzes-of-early-factors-in-midbrain-differentiation-programs
#14
Simone Mesman, Sonja J Krüse, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are born in the ventricular zone (VZ) of the midbrain between E10 and E12. Although these neurons all express specific DA markers like Th and Pitx3, they are subdivided into distinct subsets, each depending on a unique set of transcription factors and signaling cascades for their differentiation. How a neural progenitor commits to an mdDA neuronal cell-fate and how the specification into the different subsets is determined remains unclear. To gain more insight into the development and specification of these neurons we have previously conducted a genome-wide expression analysis, in which dissected midbrain material (E10...
September 27, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28949038/parkinsonism-without-dopamine-neuron-degeneration-in-aged-l-dopa-responsive-dystonia-knockin-mice
#15
Samuel J Rose, Porter Harrast, Christine Donsante, Xueliang Fan, Valerie Joers, Malú G Tansey, H A Jinnah, Ellen J Hess
BACKGROUND: Recent neuroimaging studies implicate nigrostriatal degeneration as a critical factor in producing late-onset parkinsonism in patients with l-dopa-responsive dystonia-causing mutations. However, postmortem anatomical studies do not reveal neurodegeneration in l-dopa-responsive dystonia patients. These contrasting findings make it unclear how parkinsonism develops in l-dopa-responsive dystonia mutation carriers. METHODS: We prospectively assessed motor dysfunction, responses to dopaminergic challenge, and dopamine neuron degeneration with aging in a validated knockin mouse model bearing a l-dopa-responsive dystonia-causing mutation found in humans...
September 26, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28945746/proteasome-impairment-by-%C3%AE-synuclein
#16
Lisa Zondler, Marcus Kostka, Patrick Garidel, Udo Heinzelmann, Bastian Hengerer, Benjamin Mayer, Jochen H Weishaupt, Frank Gillardon, Karin M Danzer
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide and characterized by the loss of dopaminergic neurons in the patients' midbrains. Both the presence of the protein α-synuclein in intracellular protein aggregates in surviving neurons and the genetic linking of the α-synuclein encoding gene point towards a major role of α-synuclein in PD etiology. The exact pathogenic mechanisms of PD development are not entirely described to date, neither is the specific role of α-synuclein in this context...
2017: PloS One
https://www.readbyqxmd.com/read/28943253/iap-based-cell-sorting-results-in-homogeneous-transplantable-dopaminergic-precursor-cells-derived-from-human-pluripotent-stem-cells
#17
Daniela Lehnen, Serena Barral, Tiago Cardoso, Shane Grealish, Andreas Heuer, Andrej Smiyakin, Agnete Kirkeby, Jutta Kollet, Harold Cremer, Malin Parmar, Andreas Bosio, Sebastian Knöbel
Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28928221/up-regulation-of-autophagy-related-gene-5-atg5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#18
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911883/tnf-superfamily-member-april-enhances-midbrain-dopaminergic-axon-growth-and-contributes-to-the-nigrostriatal-projection-in-vivo
#19
Thomas G McWilliams, Laura Howard, Sean Wyatt, Alun M Davies
We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages. The axon growth-enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons...
December 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28882997/dopamine-oxidation-mediates-mitochondrial-and-lysosomal-dysfunction-in-parkinson-s-disease
#20
Lena F Burbulla, Pingping Song, Joseph R Mazzulli, Enrico Zampese, Yvette C Wong, Sohee Jeon, David P Santos, Judith Blanz, Carolin D Obermaier, Chelsee Strojny, Jeffrey N Savas, Evangelos Kiskinis, Xiaoxi Zhuang, Rejko Krüger, D James Surmeier, Dimitri Krainc
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation...
September 22, 2017: Science
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