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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28103901/pathogenic-lrrk2-variants-are-gain-of-function-mutations-that-enhance-lrrk2-mediated-repression-of-%C3%AE-catenin-signaling
#1
Daniel C Berwick, Behzad Javaheri, Andrea Wetzel, Mark Hopkinson, Jonathon Nixon-Abell, Simone Grannò, Andrew A Pitsillides, Kirsten Harvey
BACKGROUND: LRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson's disease, while recent studies have identified potential protective variants. This, and the fact that LRRK2 mutation carriers develop symptoms and brain pathology almost indistinguishable from idiopathic Parkinson's disease, has led to enormous interest in this protein. LRRK2 has been implicated in a range of cellular events, but key among them is canonical Wnt signalling, which results in increased levels of transcriptionally active β-catenin...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#2
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/28094017/predictive-markers-guide-differentiation-to-improve-graft-outcome-in-clinical-translation-of-hesc-based-therapy-for-parkinson-s-disease
#3
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/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#4
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
#5
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/28069917/dopamine-modulates-the-functional-organization-of-the-orbitofrontal-cortex
#6
Thorsten Kahnt, Philippe N Tobler
: Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons, and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain, and thereby reconfigures functional networks in the OFC...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28068941/looking-beyond-the-brain-to-improve-the-pathogenic-understanding-of-parkinson-s-disease-implications-of-whole-transcriptome-profiling-of-patients-skin
#7
Anu Planken, Lille Kurvits, Ene Reimann, Liis Kadastik-Eerme, Külli Kingo, Sulev Kõks, Pille Taba
BACKGROUND: Parkinson's Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, however non-neuronal symptoms are also common. Although great advances have been made in the pathogenic understanding of Parkinson's Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. In addition, a higher rate of melanoma and non-melanoma skin cancer has been observed in the Parkinson's Disease population, indicating crosstalk between these diseases...
January 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28061349/seq-ing-markers-of-midbrain-dopamine-neurons
#8
Teresia Osborn, Penelope J Hallett
Transplantation of human pluripotent stem cell-derived dopaminergic neurons is a promising approach to treating Parkinson's disease. In this issue of Cell Stem Cell, Kee et al. (2017) and Kirkeby et al. (2017) identify specific markers of midbrain dopaminergic progenitors to improve their derivation and predict dopamine neuron content after engraftment.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28057299/mechanisms-of-parkinson-s-disease-lessons-from-drosophila
#9
V L Hewitt, A J Whitworth
The power of Drosophila genetics has attracted attention in tackling important biomedical challenges such as the understanding and prevention of neurodegenerative diseases. Parkinson's disease (PD) is the most common neurodegenerative movement disorder which results from the relentless degeneration of midbrain dopaminergic neurons. Over the past two decades tremendous advances have been made in identifying genes responsible for inherited forms of PD. The ease of genetic manipulation in Drosophila has spurred the development of numerous models of PD, including expression of human genes carrying pathogenic mutations or the targeted mutation of conserved orthologs...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28053028/activation-of-pedunculopontine-glutamate-neurons-is-reinforcing
#10
Ji Hoon Yoo, Vivien Zell, Johnathan Wu, Cindy Punta, Nivedita Ramajayam, Xinyi Shen, Lauren Faget, Varoth Lilascharoen, Byung Kook Lim, Thomas S Hnasko
: Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28042822/enduring-sexually-dimorphic-impact-of-in-utero-exposure-to-elevated-levels-of-glucocorticoids-on-midbrain-dopaminergic-populations
#11
REVIEW
Glenda E Gillies, Kanwar Virdee, Ilse Pienaar, Felwah Al-Zaid, Jeffrey W Dalley
Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life...
December 30, 2016: Brain Sciences
https://www.readbyqxmd.com/read/28042095/reduced-noradrenergic-innervation-of-ventral-midbrain-dopaminergic-cell-groups-and-the-subthalamic-nucleus-in-mptp-treated-parkinsonian-monkeys
#12
Gunasingh Jeyaraj Masilamoni, Olivia Groover, Yoland Smith
There is anatomical and functional evidence that ventral midbrain dopaminergic (DA) cell groups and the subthalamic nucleus (STN) receive noradrenergic innervation in rodents, but much less is known about these interactions in primates. Degeneration of NE neurons in the locus coeruleus (LC) and related brainstem NE cell groups is a well-established pathological feature of Parkinson's disease (PD), but the development of such pathology in animal models of PD has been inconsistent across species and laboratories...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28028942/effects-of-propofol-on-the-liver-oxidative-antioxidant-balance-in-a-rat-model-of-parkinson-s-disease
#13
Ewa B Romuk, Wioletta Szczurek, Przemysław G Nowak, Edyta Hudziec, Ewa Chwalińska, Ewa Birkner
BACKGROUND: Parkinson's disease is caused by the destruction of dopaminergic neurons in the substantia nigra of the midbrain. One of the possible factors involved in the pathogenesis of Parkinson's disease is impaired oxidativeantioxidative balance. OBJECTIVES: The present study aimed to evaluate selected parameters of the liver oxidative-antioxidative system in a Wistar rat model with Parkinson's disease treated with propofol. MATERIAL AND METHODS: Experiments were performed on 32 rats divided into 4 groups: 1 - control, 2 - Parkinson's disease, 3 - control with propofol, 4 - Parkinson's disease with propofol...
September 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28011073/behavioral-effects-and-neuroanatomical-targets-of-acute-atrazine-exposure-in-the-male-sprague-dawley-rat
#14
V M Rodriguez, M S Mendoza-Trejo, I Hernandez-Plata, M Giordano
Atrazine (ATR) is an herbicide broadly used in the world to control weeds in corn and sorghum fields, and it is potentially toxic for the dopaminergic system. Alterations in dopaminergic markers after ATR administration in rats and C57BL/6 mice have been reported. Behaviorally, it has been observed that ATR exposure causes hypoactivity shortly after its administration. To understand how acute ATR administration induces hypoactivity, we set out to map the brain areas responsive to ATR using c-Fos as a marker of neuronal activity, and tyrosine hydroxylase (TH) as a marker of dopaminergic neurons...
December 21, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/28009292/tgf-%C3%AE-signaling-in-dopaminergic-neurons-regulates-dendritic-growth-excitatory-inhibitory-synaptic-balance-and-reversal-learning
#15
Sarah X Luo, Leah Timbang, Jae-Ick Kim, Yulei Shang, Kadellyn Sandoval, Amy A Tang, Jennifer L Whistler, Jun B Ding, Eric J Huang
Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28000847/pi3k-akt-signaling-mediated-by-g%C3%A2-protein%C3%A2-coupled-receptors-is-involved-in-neurodegenerative-parkinson-s-disease-review
#16
Noriko Nakano, Satoru Matsuda, Mayuko Ichimura, Akari Minami, Mako Ogino, Toshiyuki Murai, Yasuko Kitagishi
Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. Motor deficits in PD are due mostly to the progressive loss of nigrostriatal dopaminergic neurons. Neuroprotection of functional neurons is of significance in the treatment of PD...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27965546/spatial-and-temporal-distribution-of-dopaminergic-neurons-during-development-in-zebrafish
#17
Yuchen Du, Qiang Guo, Minghui Shan, Yongmei Wu, Sizhou Huang, Haixia Zhao, Huarong Hong, Ming Yang, Xi Yang, Liyi Ren, Jiali Peng, Jing Sun, Hongli Zhou, Shurong Li, Bingyin Su
As one of the model organisms of Parkinson's disease (PD) research, the zebrafish has its advantages, such as the 87% homology with human genome and transparent embryos which make it possible to observe the development of dopaminergic neurons in real time. However, there is no midbrain dopaminergic system in zebrafish when compared with mammals, and the location and projection of the dopaminergic neurons are seldom reported. In this study, Vmat2:GFP transgenic zebrafish was used to observe the development and distribution of dopaminergic neurons in real time...
2016: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/27960106/aldose-reductase-deficiency-leads-to-oxidative-stress-induced-dopaminergic-neuronal-loss-and-autophagic-abnormality-in-an-animal-model-of-parkinson-s-disease
#18
Patrick K K Yeung, Angela K W Lai, Hyo Jin Son, Xu Zhang, Onyou Hwang, Stephen S M Chung, Sookja K Chung
Fungicide exposure causes degeneration of dopaminergic neurons and contributes to Parkinson's disease (PD). Benomyl inhibits enzymes responsible for detoxifying the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. Aldose reductase (AR) is known as tetrahydrobiopterin (BH4) reductase that generates BH4, a cofactor for tyrosine hydroxylase (TH) involved in dopamine synthesis. AR also acts as an aldehyde reductase involved in detoxifying 3,4-dihydroxyphenylacetaldehyde. In PD patients, the level of AR is significantly lower in the cerebellum...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27938488/a-subpopulation-of-dopaminergic-neurons-co-expresses-serotonin-in-ventral-mesencephalic-cultures-but-not-after-intrastriatal-transplantation-in-a-rat-model-of-parkinsons-disease
#19
Stefano Di Santo, Stefanie Seiler, Angélique Ducray, Morten Meyer, Hans Widmer
Cell replacement therapy is a promising avenue into the investigation and treatment of Parkinson’s disease (PD) and in some cases significant long-term motor improvements have been demonstrated. The main source of donor tissue is the human fetal ventral mesencephalon (VM), which consists of a mixed neuronal population and its heterogeneity likely contributes to the inconsistent outcome observed in clinical trials. Detailed knowledge about the neuronal subpopulations in the VM seems, hence, essential for successful cell transplantation...
7, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27928028/mitochondrial-pyruvate-carrier-regulates-autophagy-inflammation-and-neurodegeneration-in-experimental-models-of-parkinson-s-disease
#20
Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N Hildebrandt, Jennifer A Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, William G McDonald, Martha L Escobar Galvis, Jeffrey H Kordower, Jeremy M Van Raamsdonk, Jerry R Colca, Patrik Brundin
Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP(+)) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model...
December 7, 2016: Science Translational Medicine
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