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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28547771/translation-of-wnt-developmental-programs-into-stem-cell-replacement-strategies-for-the-treatment-of-parkinson-s-disease
#1
REVIEW
Enrique M Toledo, Daniel Gyllborg, Ernest Arenas
Wnt signalling is a highly conserved pathway across species that is critical for normal development and is deregulated in multiple diseases including cancer and neurodegeneration. Wnt signalling is critically required for midbrain dopaminergic (mDA) neuron development and maintenance. Understanding the molecular processes controlled by Wnt signalling may thus hold the key to understand the physiopathology and to develop novel therapies aimed at preventing the loss of mDA neurons in Parkinson's disease (PD)...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28543594/the-neuroprotective-role-of-mir-124-3p-in-a-6-hydroxydopamine-induced-cell-model-of-parkinson-s-disease-via-the-regulation-of-anax5
#2
Rui-Fang Dong, Bing Zhang, Li-Wen Tai, Hong-Mei Liu, Fang-Kun Shi, Ning-Ning Liu
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Several pathogenetic factors have been involved in the onset and progression of PD, including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Ample evidence indicates that miRNAs could regulate post-transcriptional gene expression and neuronal disease. In this study, we evaluated the effects and mechanism of miR-124-3p on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and SH-SY5Y cells...
May 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28539529/membrane-trafficking-illuminates-a-path-to-parkinson-s-disease
#3
Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki
Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28535980/nogo-receptor-1-antagonization-in-combination-with-neurotrophin-4-5-is-not-superior-to-single-factor-treatment-in-promoting-survival-and-morphological-complexity-of-cultured-dopaminergic-neurons
#4
Stefanie Seiler, Stefano Di Santo, Sebastian Sahli, Lukas Andereggen, Hans Rudolf Widmer
Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures...
May 20, 2017: Brain Research
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#5
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28507136/ocd-candidate-gene-slc1a1-eaat3-impacts-basal-ganglia-mediated-activity-and-stereotypic-behavior
#6
Isaac D Zike, Muhammad O Chohan, Jared M Kopelman, Emily N Krasnow, Daniel Flicker, Katherine M Nautiyal, Michael Bubser, Christoph Kellendonk, Carrie K Jones, Gregg Stanwood, Kenji Fransis Tanaka, Holly Moore, Susanne E Ahmari, Jeremy Veenstra-VanderWeele
Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1)...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28506618/the-ptz-kindling-mouse-model-of-epilepsy-exhibits-exploratory-drive-deficits-and-aberrant-vta-dopamine-neuron-activity-in-both-familiar-and-novel-space
#7
Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#8
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28504367/neuroprotective-natural-products-for-the-treatment-of-parkinson-s-disease-by-targeting-the-autophagy-lysosome-pathway-a-systematic-review
#9
REVIEW
Zi-Ying Wang, Jing-Yi Liu, Chuan-Bin Yang, Sandeep Malampati, Ying-Yu Huang, Mei-Xiang Li, Min Li, Ju-Xian Song
The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment...
May 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28504195/fgf18-protects-against-6-hydroxydopamine-induced-nigrostriatal-damage-in-a-rat-model-of-parkinson-s-disease
#10
Xingzhi Guo, Tingting Liu, Diandian Zhao, Xiaofeng Wang, Dongmei Liu, Yang He, Chang Shan, Yingying Kong, Weiwei Hu, Bei Tao, Lihao Sun, Hongyan Zhao, Shengtian Li, Jianmin Liu
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway...
May 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28473257/stress-and-corticosterone-alter-synaptic-plasticity-in-a-rat-model-of-parkinson-s-disease
#11
YongXin Hao, Aref Shabanpoor, Gerlinde A Metz
As a major influence on neuronal function and plasticity, chronic stress can affect the progression and symptoms of neurodegenerative conditions, such as Parkinson's disease (PD). Here we investigated the influence of unilateral dopamine depletion and stress on dopamine-related hallmarks of stress response and neuronal plasticity in a rat model of PD. Animals received either restraint stress or a combination of adrenalectomy and corticosterone (CORT) supplementation to clamp circulating glucocorticoid levels for three weeks prior to unilateral nigrostriatal dopamine depletion...
May 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28472632/the-involvement-of-brain-derived-neurotrophic-factor-in-3-4-methylenedioxymethamphetamine-induced-place-preference-and-behavioral-sensitization
#12
Akihiro Mouri, Yukihiro Noda, Minae Niwa, Yurie Matsumoto, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Shoei Furukawa, Tatsunori Iwamura, Toshitaka Nabeshima
3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus...
May 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28468332/neuroprotective-role-of-atractylenolide-i-in-an-in-vitro-and-in-vivo-model-of-parkinson-s-disease
#13
Sandeep More, Dong-Kug Choi
Parkinson's disease (PD) is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I) in in vivo and in vitro models of PD...
May 2, 2017: Nutrients
https://www.readbyqxmd.com/read/28467897/dopamine-induces-oscillatory-activities-in-human-midbrain-neurons-with-parkin-mutations
#14
Ping Zhong, Zhixing Hu, Houbo Jiang, Zhen Yan, Jian Feng
Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolishes the oscillatory activities in patient neurons...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28452458/chiro-optical-modulation-for-nurr1-production-from-stem-cells
#15
Madhumita Patel, Hyo Jung Moon, Ja Hye Hong, Byeongmoon Jeong
Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's disease. To enhance the NURR1 production of neural cells, various approaches are under investigation. Here we report that NURR1 is highly expressed in stem cells by exposure to an L-polarized blue light emitting diode (LED). Compared to stem cells cultured in the absence of a LED, under polarized green and red LEDs, the stem cells exposed to a polarized blue LED significantly enhanced neuronal biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at both mRNA and protein levels...
May 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28450060/endocannabinoid-modulation-of-dopamine-neurotransmission
#16
REVIEW
Dan Covey, Yolanda Mateo, David Sulzer, Joseph F Cheer, David M Lovinger
Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain that controls neural circuits involved in the cognitive, emotional, and motor aspects of goal-directed behavior. Accordingly, perturbations in DA neurotransmission play a central role in several neuropsychiatric disorders. Somewhat surprisingly given its prominent role in numerous behaviors, DA is released by a relatively small number of densely packed neurons originating in the midbrain. The dopaminergic midbrain innervates numerous brain regions where extracellular DA release and receptor binding promote short- and long-term changes in postsynaptic neuron function...
April 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28443089/japanese-encephalitis-virus-exploits-dopamine-d2-receptor-phospholipase-c-to-target-dopaminergic-human-neuronal-cells
#17
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
#18
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
#19
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
#20
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
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