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Midbrain dopaminergic neuron

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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/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
#2
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/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#3
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/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#4
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/29311261/towards-stem-cell-based-therapies-for-parkinson-s-disease
#5
Malin Parmar
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming...
January 8, 2018: Development
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#6
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29289371/glucose-modulates-human-ventral-tegmental-activity-in-response-to-sexual-stimuli
#7
Martin Ulrich, Philipp Stauß, Georg Grön
BACKGROUND: Attribution of salience to sexual stimuli is mediated by the dopaminergic midbrain, including the ventral tegmental area (VTA). The existence of glucose-sensing neurons in the VTA, as suggested by animal studies, offers the opportunity to modulate aberrant salience coding involved in sexual disorders such as sexual addiction. Recent neuroimaging work supported that VTA activity in humans can be modulated by intravenously infusing a small bolus of glucose. However, that study used appetitive food stimuli, leaving the possibility that glucose modulation of VTA-mediated salience coding might be bound to this class of stimuli...
January 2018: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29276478/application-of-the-physical-disector-principle-for-quantification-of-dopaminergic-neuronal-loss-in-a-rat-6-hydroxydopamine-nigral-lesion-model-of-parkinson-s-disease
#8
Katrine Fabricius, Pernille Barkholt, Jacob Jelsing, Henrik H Hansen
Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29244806/cellular-selectivity-of-aav-serotypes-for-gene-delivery-in-neurons-and-astrocytes-by-neonatal-intracerebroventricular-injection
#9
Sean L Hammond, Ashley N Leek, Evan H Richman, Ronald B Tjalkens
The non-pathogenic parvovirus, adeno-associated virus (AAV), is an efficient vector for transgene expression in vivo and shows promise for treatment of brain disorders in clinical trials. Currently, there are more than 100 AAV serotypes identified that differ in the binding capacity of capsid proteins to specific cell surface receptors that can transduce different cell types and brain regions in the CNS. In the current study, multiple AAV serotypes expressing a GFP reporter (AAV1, AAV2/1, AAVDJ, AAV8, AAVDJ8, AAV9, AAVDJ9) were screened for their infectivity in both primary murine astrocyte and neuronal cell cultures...
2017: PloS One
https://www.readbyqxmd.com/read/29236052/micrornas-in-parkinson-s-disease-from-pathogenesis-to-novel-diagnostic-and-therapeutic-approaches
#10
REVIEW
Loredana Leggio, Silvia Vivarelli, Francesca L'Episcopo, Cataldo Tirolo, Salvo Caniglia, Nunzio Testa, Bianca Marchetti, Nunzio Iraci
Parkinson's disease (PD) is the most prevalent central nervous system (CNS) movement disorder and the second most common neurodegenerative disease overall. PD is characterized by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) within the midbrain, accumulation of alpha-synuclein (α-SYN) in Lewy bodies and neurites and excessive neuroinflammation. The neurodegenerative processes typically begin decades before the appearance of clinical symptoms. Therefore, the diagnosis is achievable only when the majority of the relevant DAergic neurons have already died and for that reason available treatments are only palliative at best...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29234141/cannabinoid-type-2-receptors-in-dopamine-neurons-inhibits-psychomotor-behaviors-alters-anxiety-depression-and-alcohol-preference
#11
Qing-Rong Liu, Ana Canseco-Alba, Hai-Ying Zhang, Patricia Tagliaferro, Monika Chung, Eugene Dennis, Branden Sanabria, Norman Schanz, Joao Carlos Escosteguy-Neto, Hiroki Ishiguro, Zhicheng Lin, Susan Sgro, Claire M Leonard, Jair Guilherme Santos-Junior, Eliot L Gardner, Josephine M Egan, Jeung Woon Lee, Zheng-Xiong Xi, Emmanuel S Onaivi
Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229347/post-operative-stridor-and-acute-respiratory-failure-after-parkinson-s-disease-deep-brain-stimulator-placement-a-case-report-and-review-of-literature
#12
Mi Wang, Wael Saasouh, Thomas Botsford, Allen Keebler, Andrew Zura, Michael S Benninger, Rafi Avitsian
BACKGROUND: Parkinson's disease (PD), a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra of the midbrain is commonly thought of as a motion disorder, but it can have significant effect on the respiratory system. Respiratory failure is the most common cause of death in these patients, but it can also affect laryngeal function causing dysphonia, dysphagia, and dysarthric speech.. Acute upper airway obstruction is a very rare finding in PD, especially in the perioperative settings...
December 8, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29217488/incomplete-concordance-of-dopamine-transporter-cre-datirescre-mediated-recombination-and-tyrosine-hydroxylase-immunoreactivity-in-the-mouse-forebrain
#13
Siew Hoong Yip, Jade York, Brian Hyland, Stephen J Bunn, David R Grattan
Co-localization of the expression of the dopamine transporter (DAT) with the catecholamine synthesising enzyme tyrosine hydroxylase (TH) has been investigated using transgenic mice expressing Cre recombinase (Cre) dependent green fluorescent protein (GFP) under the control of the DAT promoter (DATIREScre/GFP). Brain sections from adult female mice were stained for Cre-induced GFP and TH using immunohistochemistry, revealing a high degree of co-expression in the midbrain dopaminergic neurons (A8-10) with the exception of the periaqueductal and dorsal raphe nuclei where dual-labelling was notably lower...
December 4, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29196028/serum-response-factor-promotes-dopaminergic-neuron-survival-via-activation-of-beclin-1-dependent-autophagy
#14
Xiao-Yu Cheng, Si-Yue Li, Cheng-Jie Mao, Mei-Xia Wang, Jing Chen, Fen Wang, Guang-Hui Wang, Wen-Bin Deng, Xiao-Kang Li, Chun-Feng Liu
Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons...
November 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29188488/lipopolysaccharide-induced-microglia-activation-promotes-the-survival-of-midbrain-dopaminergic-neurons-in-vitro
#15
Xiaolai Zhou, Björn Spittau
Microglia are the resident immune cells of the central nervous system (CNS) and respond to a variety of endogenous and exogenous stimuli in order to restore cell and tissue homeostasis. Lipopolysaccharide (LPS) is one of these exogenous stimuli, constitutes a major component of the outer membrane of Gram-negative bacteria, and binds to the microglial pattern recognition receptor Toll-like receptor 4 (TLR4). LPS-induced microglia activation is believed to promote neurodegeneration by release of neurotoxic factors such as interleukin-1β, tumor necrosis factor α, or nitric oxide...
November 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29183158/critical-roles-of-glutaredoxin-in-brain-cells-implications-for-parkinson-s-disease
#16
Olga Gorelenkova Miller, John J Mieyal
SIGNIFICANCE: Glutaredoxin (Grx1), an evolutionarily conserved and ubiquitous enzyme, regulates redox signal transduction and protein redox homeostasis by catalyzing reversible S-glutathionylation. Grx1 plays different roles in different cell types. In Parkinson's disease (PD), Grx1 regulates apoptosis signaling in dopaminergic neurons, so that loss of Grx1 leads to increased cell death; in microglial cells, Grx1 regulates pro-inflammatory signaling, so that upregulation of Grx1 promotes cytokine production...
November 28, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29177188/%C3%AE-synuclein-dependent-calcium-entry-underlies-differential-sensitivity-of-cultured-sn-and-vta-dopaminergic-neurons-to-a-parkinsonian-neurotoxin
#17
Ori J Lieberman, Se Joon Choi, Ellen Kanter, Anastasia Saverchenko, Micah D Frier, Giulia M Fiore, Min Wu, Jyothisri Kondapalli, Enrico Zampese, D James Surmeier, David Sulzer, Eugene V Mosharov
Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by a loss of dopaminergic neurons in the substantia nigra (SN). Although mitochondrial dysfunction and dysregulated α-synuclein (aSyn) expression are postulated to play a role in PD pathogenesis, it is still debated why neurons of the SN are targeted while neighboring dopaminergic neurons of the ventral tegmental area (VTA) are spared. Using electrochemical and imaging approaches, we investigated metabolic changes in cultured primary mouse midbrain dopaminergic neurons exposed to a parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+)...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29175031/dopamine-neuron-loss-by-selective-deletion-of-autophagy-related-gene-5-is-not-exacerbated-by-mptp-toxicity-in-midbrain
#18
Yan-Hua Ren, Xue-Yuan Niu, Hou-Ju Huang, Xiao-Di Hao, Peng-Xiang Wang, Yi-Li Chi, Yu-Qiang Ding, Min Liao
Parkinson's disease (PD) is a progressive neurological disease, one of the pathological characteristics is a gradual loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNpc). In animals, PD-like symptoms can be induced by genetic mutations or by neurotoxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). It has been reported that deletion of autophagy-related gene 5 (Atg5) in the brain can disrupt neural function and is accompanied by the accumulation of cytoplasmic inclusions...
November 22, 2017: Neuroscience Letters
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
#19
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
#20
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
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