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https://www.readbyqxmd.com/read/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#1
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339481/repetitive-aggressive-encounters-generate-a-long-lasting-internal-state-in-drosophila-melanogaster-males
#2
Yong-Kyu Kim, Mathias Saver, Jasper Simon, Clement F Kent, Lisha Shao, Mark Eddison, Pavan Agrawal, Michael Texada, James W Truman, Ulrike Heberlein
Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339319/treatment-with-the-noradrenaline-re-uptake-inhibitor-atomoxetine-alone-and-in-combination-with-the-%C3%AE-2-adrenoceptor-antagonist-idazoxan-attenuates-loss-of-dopamine-and-associated-motor-deficits-in-the-lps-inflammatory-rat-model-of-parkinson-s-disease
#3
Justin D Yssel, Eoin O'Neill, Yvonne M Nolan, Thomas J Connor, Andrew Harkin
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment...
January 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29339106/safinamide-a-new-hope-for-parkinson-s-disease
#4
REVIEW
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
January 12, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#5
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#6
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes are controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337144/early-activation-of-egr-1-promotes-neuroinflammation-and-dopaminergic-neurodegeneration-in-an-experimental-model-of-parkinson-s-disease
#7
Qing Yu, Qiaoying Huang, Xiaoxiao Du, Shao Xu, Mingtao Li, Shanshan Ma
The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction of Egr-1 in the SNpc but not in the striatum...
January 11, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29337137/basal-mitophagy-occurs-independently-of-pink1-in-mouse-tissues-of-high-metabolic-demand
#8
Thomas G McWilliams, Alan R Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M K Muqit, Simon P Brooks, Ian G Ganley
Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#9
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29332269/behavioral-biochemical-and-molecular-characterization-of-a-parkinson-s-disease-mouse-model-using-the-neurotoxin-2-ch3-mptp-a-novel-approach
#10
Alice Laschuk Herlinger, Agihane Rodrigues Almeida, Sarah Martins Presti-Silva, Evaldo Vitor Pereira, Filipe Andrich, Rita Gomes Wanderley Pires, Cristina Martins-Silva
The neurotoxin MPTP has long been used to create a mouse model of Parkinson's disease (PD). Indeed, several MPTP analogues have been developed, including 2'-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated...
January 13, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29331709/what-do-the-genetic-association-data-say-about-the-high-risk-of-suicide-in-people-with-depression-a-novel-network-based-approach-to-find-common-molecular-basis-for-depression-and-suicidal-behavior-and-related-therapeutic-targets
#11
Ali Bozorgmehr, Fatemeh Alizadeh, Sattar Norouzi Ofogh, Mohammad Reza Abdollahzadeh Hamzekalayi, Sara Herati, Atefeh Moradkhani, Ali Shahbazi, Mohammad Ghadirivasfi
BACKGROUND: Available sources indicate that the risk of suicide in people with major depression is higher than other psychiatric disorders. Although it seems that these two conditions may have a shared cause in some cases, no studies have been conducted to identify a common basis for them. METHODS: In this study, following an extensive review of literature, we found almost all the genes that are involved in major depression and suicidal behavior, and we isolated genes shared between the two conditions...
January 8, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29330488/motor-skill-learning-and-reward-consumption-differentially-affect-vta-activation
#12
Susan Leemburg, Tara Canonica, Andreas Luft
Dopamine release from the ventral tegmental area (VTA) terminals in the primary motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis that dopaminergic VTA neurons projecting to M1 are activated when rewards are obtained during motor skill acquisition, but not during task execution at plateau performance, or by rewards obtained without performing skilled movements. Rats were trained to perform a skilled reaching task for 3 days (acquisition) or 7 days (plateau). In combination with retrograde labelling of VTA-to-M1 projection neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was used to assess activation of dopaminergic and non-dopaminergic VTA neurons...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#13
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29325757/the-role-of-fatty-acids-and-their-endocannabinoid-like-derivatives-in-the-molecular-regulation-of-appetite
#14
REVIEW
Renger F Witkamp
Intake, absorption and synthesis of fatty acids, including those produced by the intestinal microbiota are tightly monitored via specific receptors and, indirectly through their conversion into a variety of signalling molecules. The resulting information is integrated and translated to different physiological processes, including the regulation of appetite and satiation. Direct chemosensing of fatty acids takes place via interaction with free fatty acid (FFA) and other receptors. These are present in the oronasal cavity and along the entire gastrointestinal tract, in various other tissues, and, for some receptors also in brain...
January 8, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29323027/micrornas-in-parkinson-s-disease-and-emerging-therapeutic-targets
#15
REVIEW
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29322941/persistent-activity-in-a-recurrent-circuit-underlies-courtship-memory-in-drosophila
#16
Xiaoliang Zhao, Daniela Lenek, Ugur Dag, Barry Dickson, Krystyna Keleman
Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBg), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ>M6 synapses over time periods that match short-term memory...
January 11, 2018: ELife
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#17
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29314192/parvalbumin-producing-striatal-interneurons-receive-excitatory-inputs-onto-proximal-dendrites-from-the-motor-thalamus-in-male-mice
#18
Yasutake Nakano, Fuyuki Karube, Yasuharu Hirai, Kenta Kobayashi, Hiroyuki Hioki, Shinichiro Okamoto, Hiroshi Kameda, Fumino Fujiyama
In rodents, the dorsolateral striatum regulates voluntary movement by integrating excitatory inputs from the motor-related cerebral cortex and thalamus to produce contingent inhibitory output to other basal ganglia nuclei. Striatal parvalbumin (PV)-producing interneurons receiving this excitatory input then inhibit medium spiny neurons (MSNs) and modify their outputs. To understand basal ganglia function in motor control, it is important to reveal the precise synaptic organization of motor-related cortical and thalamic inputs to striatal PV interneurons...
January 4, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#19
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311646/generation-of-functional-dopaminergic-neurons-from-reprogramming-fibroblasts-by-nonviral-based-mesoporous-silica-nanoparticles
#20
Jen-Hsuan Chang, Ping-Hsing Tsai, Kai-Yi Wang, Yu-Ting Wei, Shih-Hwa Chiou, Chung-Yuan Mou
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons)...
January 8, 2018: Scientific Reports
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