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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28443089/japanese-encephalitis-virus-exploits-dopamine-d2-receptor-phospholipase-c-to-target-dopaminergic-human-neuronal-cells
#1
Yogy Simanjuntak, Jian-Jong Liang, Yi-Ling Lee, Yi-Ling Lin
Despite the availability of vaccines for Japanese encephalitis virus (JEV), the re-emerging virus remains a clinically important pathogen that causes acute encephalitis and permanent neuropsychiatric sequels. JEV highly targets dopaminergic neuron-rich brain regions including the thalamus and midbrain. The molecular mechanism contributing to the high susceptibility of these particular brain regions remains largely unclear. This study addressed whether this tissue tropism of JEV is associated with signaling of dopaminergic neurons...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28442947/a-high-fat-diet-induces-a-loss-of-midbrain-dopaminergic-neuronal-function-that-underlies-motor-abnormalities
#2
Yunseon Jang, Min Joung Lee, Jeongsu Han, Soo Jeong Kim, Ilhwan Ryu, Xianshu Ju, Min Jeong Ryu, Woosuk Chung, Eungseok Oh, Gi Ryang Kweon, Jun Young Heo
Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the striatum is responsible for regulating grip strength and motor initiation through tyrosine hydroxylase (TH) activity-dependent dopamine release...
April 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28439401/long-non-coding-rna-malat1-contributes-to-cell-apoptosis-by-sponging-mir-124-in-parkinson-disease
#3
Wei Liu, Qishun Zhang, Jianlei Zhang, Wujun Pan, Jingya Zhao, Yuming Xu
BACKGROUND: Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined. METHODS: The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP(+)) were utilized to investigate the effect of MALAT1 on PD...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28424350/tau-haploinsufficiency-causes-prenatal-loss-of-dopaminergic-neurons-in-the-ventral-tegmental-area-and-reduction-of-transcription-factor-orthodenticle-homeobox-2-expression
#4
Meige Zheng, Luyan Jiao, Xiaolu Tang, Xianhong Xiang, Xiaomei Wan, Yan Yan, Xingjian Li, Guofeng Zhang, Yonglin Li, Bin Jiang, Huaibin Cai, Xian Lin
Homozygous tau knockout (Mapt(-/-)) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt(+/-)) pups, but not a complete loss of tau in the Mapt(-/-) littermates, led to a significant reduction of DA neurons in the VTA...
April 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28420965/dopamine-a-modulator-of-circadian-rhythms-in-the-central-nervous-system
#5
REVIEW
Kirill S Korshunov, Laura J Blakemore, Paul Q Trombley
Circadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28419831/molecular-phenotyping-of-transient-postnatal-tyrosine-hydroxylase-neurons-in-the-rat-bed-nucleus-of-the-stria-terminalis
#6
David A Carter
The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype...
April 15, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28416282/derivation-of-human-midbrain-specific-organoids-from-neuroepithelial-stem%C3%A2-cells
#7
Anna S Monzel, Lisa M Smits, Kathrin Hemmer, Siham Hachi, Edinson Lucumi Moreno, Thea van Wuellen, Javier Jarazo, Jonas Walter, Inga Brüggemann, Ibrahim Boussaad, Emanuel Berger, Ronan M T Fleming, Silvia Bolognin, Jens C Schwamborn
Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation...
March 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28401925/menthol-enhances-nicotine-reward-related-behavior-by-potentiating-nicotine-induced-changes-in-nachr-function-nachr-upregulation-and-da-neuron-excitability
#8
Brandon J Henderson, Teagan R Wall, Beverley M Henley, Charlene H Kim, Sheri McKinney, Henry A Lester
Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone...
April 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28400256/n-oleoyldopamine-modulates-activity-of-midbrain-dopaminergic-neurons-through-multiple-mechanisms
#9
Olga A Sergeeva, Roberto De Luca, Karolina Mazur, Aissa N Chepkova, Helmut L Haas, Andreas Bauer
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed...
April 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28400118/pre-clinical-therapeutic-development-of-a-series-of-metalloporphyrins-for-parkinson-s-disease
#10
Li-Ping Liang, Jie Huang, Ruth Fulton, Jennifer N Pearson-Smith, Brian J Day, Manisha Patel
Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment...
April 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28385636/newborn-dopaminergic-neurons-are-associated-with-the-migration-and-differentiation-of-svz-derived-neural-progenitors-in-a-6-hydroxydopamin-injected-mouse-model
#11
M Q Xie, Z C Chen, P Zhang, H J Huang, T T Wang, Y-Q Ding, S S Qi, C Zhang, S X Chen, P Zhou, C C Shao, M Liao, C Y Sun
The use of the existing endogenous neural progenitor cells (NPCs) in the brains of adult mammalian animals is challenging for cell therapy in treating Parkinson's disease (PD). Previous studies have indicated that there is a low level of neurogenesis in the substantia nigra (SN) of adult mice. To assess the regenerative/neurogenic capacity of NPCs following an intranigral injection of 6-hydroxydopamine (6-OHDA), the proliferation and differentiation of subventricular zone (SVZ)- and midbrain-derived NPCs were investigated, and the origin of SN newborn dopaminergic neurons was traced by using Nestin-CreER(TM)::ROSA26-LacZ mice and constructing a plasmid CD133-Promoter2-Cre...
April 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28379221/nigrostriatal-interaction-in-the-aging-brain-new-therapeutic-target-for-parkinson-s-disease
#12
REVIEW
Janusz W Błaszczyk
Parkinson's disease (PD) is a progressive neurodegenerative disorder of unclear etiology and pathogenesis. Research results gathered to date support the hypothesis that the motor symptoms of the disease result from the gradual loss of midbrain dopamine neurons residing in the substantia nigra pars compacta (SNpc). Recent discoveries, however, significantly expand this knowledge indicating that the primary source of the PD pathogenesis may be located both in the SNpc as well as in the GABAergic striatum. Newly discovered striatal neurogenesis - normally a lifelong process - determines the efficiency of nigrostriatal interaction...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28367951/dopamine-neuronal-loss-contributes-to-memory-and-reward-dysfunction-in-a-model-of-alzheimer-s-disease
#13
Annalisa Nobili, Emanuele Claudio Latagliata, Maria Teresa Viscomi, Virve Cavallucci, Debora Cutuli, Giacomo Giacovazzo, Paraskevi Krashia, Francesca Romana Rizzo, Ramona Marino, Mauro Federici, Paola De Bartolo, Daniela Aversa, Maria Concetta Dell'Acqua, Alberto Cordella, Marco Sancandi, Flavio Keller, Laura Petrosini, Stefano Puglisi-Allegra, Nicola Biagio Mercuri, Roberto Coccurello, Nicola Berretta, Marcello D'Amelio
Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact...
April 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28363982/deficiency-in-neuronal-tgf-%C3%AE-signaling-leads-to-nigrostriatal-degeneration-and-activation-of-tgf-%C3%AE-signaling-protects-against-mptp-neurotoxicity-in-mice
#14
Ina Tesseur, Andy Nguyen, Betty Chang, Lulin Li, Nathaniel S Woodling, Tony Wyss-Coray, Jian Luo
Transforming growth factor-β (TGF-β) plays an important role in the development and maintenance of embryonic dopaminergic (DA) neurons in the midbrain. To study the function of TGF-β signaling in the adult nigrostriatal system, we generated transgenic mice with reduced TGF-β signaling in mature neurons. These mice display age-related motor deficits and degeneration of the nigrostriatal system. Increasing TGF-β signaling in the substantia nigra through adeno-associated virus (AAV) expressing a constitutively active type I receptor significantly reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration and motor deficits...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28353285/lrrk2-and-the-lrrktosome-at-the-crossroads-of-programmed-cell-death-clues-from-rip-kinase-relatives
#15
Hardy J Rideout, Diane B Re
Since its cloning and identification in 2004, considerable gains have been made in the understanding of the basic functionality of leucine-rich repeat kinase 2 (LRRK2), including its kinase and GTPase activities, its protein interactors and subcellular localization, and its expression in the CNS and peripheral tissues. However, the mechanism(s) by which expression of mutant forms of LRRK2 lead to the death of dopaminergic neurons of the ventral midbrain remains largely uncharacterized. Because of its complex domain structure, LRRK2 exhibits similarities with multiple protein families including ROCO proteins, as well as the RIP kinases...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28350199/a-novel-autophagy-modulator-6-bio-ameliorates-snca-%C3%AE-synuclein-toxicity
#16
S N Suresh, Aravinda K Chavalmane, Vidyadhara D J, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P Clement, Phalguni Anand Alladi, Ravi Manjithaya
Parkinson disease (PD) is a life-threatening neurodegenerative movement disorder with unmet therapeutic intervention. We have identified a small molecule autophagy modulator, 6-Bio that shows clearance of toxic SNCA/α-synuclein (a protein implicated in synucleopathies) aggregates in yeast and mammalian cell lines. 6-Bio induces autophagy and dramatically enhances autolysosome formation resulting in SNCA degradation. Importantly, neuroprotective function of 6-Bio as envisaged by immunohistology and behavior analyses in a preclinical model of PD where it induces autophagy in dopaminergic neurons of mice midbrain to clear toxic protein aggregates suggesting that it could be a potential therapeutic candidate for protein conformational disorders...
March 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#17
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28321769/n-propargyl-caffeamide-paca-ameliorates-dopaminergic-neuronal-loss-and-motor-dysfunctions-in-mptp-mouse-model-of-parkinson-s-disease-and-in-mpp-induced-neurons-via-promoting-the-conversion-of-prongf-to-ngf
#18
Dan Luo, Jia Zhao, Yuanyuan Cheng, Simon Ming-Yuen Lee, Jianhui Rong
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days...
March 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28316566/blockade-of-ryrs-in-the-er-attenuates-6-ohda-induced-calcium-overload-cellular-hypo-excitability-and-apoptosis-in-dopaminergic-neurons
#19
Lu Huang, Ying Xue, DaYun Feng, RuiXin Yang, Tiejian Nie, Gang Zhu, Kai Tao, GuoDong Gao, Qian Yang
Calcium (Ca(2+)) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca(2+) release channels and play crucial roles in regulating Ca(2+) homeostasis. However, the roles of these endogenous Ca(2+) release channels in PD and their effects on the function and survival of DA neurons remain unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#20
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
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