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https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#1
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445716/trumping-neurodegeneration-targeting-common-pathways-regulated-by-autosomal-recessive-parkinson-s-disease-genes
#2
REVIEW
Laura Scott, Valina L Dawson, Ted M Dawson
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28445713/deregulation-of-%C3%AE-synuclein-in-parkinson-s-disease-insight-from-epigenetic-structure-and-transcriptional-regulation-of-snca
#3
REVIEW
Subhrangshu Guhathakurta, Eugene Bok, Baggio A Evangelista, Yoon-Seong Kim
Understanding regulation of α-synuclein has long been a central focus for Parkinson's disease (PD) researchers. Accumulation of this protein in the Lewy body or neurites, mutations in the coding region of the gene and strong association of α-synuclein encoding gene multiplication (duplication/triplication) with familial form of PD have indicated the importance of this molecule in pathogenesis of the disease. Several years of research identified many potential faulty pathways associated with accumulation of α-synuclein inside dopaminergic neurons and its transmission to neighboring ones...
April 23, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28445429/exploring-the-behavioral-and-metabolic-phenotype-generated-by-re-introduction-of-the-ghrelin-receptor-in-the-ventral-tegmental-area
#4
Louise J Skov, Morten Jensen, Søren H Christiansen, Cecilia Ratner, David P D Woldbye, Birgitte Holst
Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R(VTA) mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions...
April 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28443637/mild-mpp-exposure-induced-glucose-starvation-enhances-autophagosome-synthesis-and-impairs-its-degradation
#5
Shuichiro Sakamoto, Masatsugu Miyara, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Parkinson's disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP(+) has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypotheses come from the studies about the acute MPP(+) exposure. We previously revealed that mild MPP(+) exposure (10 and 200 μM), which induces gradual cell death, impairs autophagosome degradation at 48 h. In the present study, we further investigated the specific events of mild MPP(+) exposure and revealed that mild MPP(+) exposure causes the cell death through glucose starvation, but not acute toxic model (2...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28443089/japanese-encephalitis-virus-exploits-dopamine-d2-receptor-phospholipase-c-to-target-dopaminergic-human-neuronal-cells
#6
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/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#7
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28442947/a-high-fat-diet-induces-a-loss-of-midbrain-dopaminergic-neuronal-function-that-underlies-motor-abnormalities
#8
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/28442946/optogenetic-rescue-of-locomotor-dysfunction-and-dopaminergic-degeneration-caused-by-alpha-synuclein-and-eko-genes
#9
Cheng Qi, Scott Varga, Soo-Jin Oh, C Justin Lee, Daewoo Lee
α-Synuclein (α-Syn) is a small presynaptic protein and its mutant forms (e.g. A53T) are known to be directly associated with Parkinson's disease (PD). Pathophysiological mechanisms underlying α-Syn-mediated neurodegeneration in PD still remain to be explored. However, several studies strongly support that overexpression of mutant α-Syn causes reduced release of dopamine (DA) in the brain, and contributes to motor deficits in PD. Using a favorable genetic model Drosophila larva, we examined whether reduced DA release is enough to induce key PD symptoms (i...
April 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28442167/tipping-points-and-endogenous-determinants-of-nigrostriatal-degeneration-by-mptp
#10
REVIEW
Stefan Schildknecht, Donato A Di Monte, Regina Pape, Kim Tieu, Marcel Leist
The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a Parkinson's disease (PD)-like syndrome by inducing degeneration of nigrostriatal dopaminergic neurons. Studies of the MPTP model have revealed the pathomechanisms underlying dopaminergic neurodegeneration and facilitated the development of drug treatments for PD. In this review, we provide an update on MPTP bioactivation and biodistribution, reconcile the distinct views on energetic failure versus reactive oxygen species (ROS) formation as main drivers of MPTP-induced neurodegeneration, and describe recently identified intrinsic features of the nigrostriatal system that make it particularly vulnerable to MPTP...
April 23, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28440808/automated-and-manual-patch-clamp-data-of-human-induced-pluripotent-stem-cell-derived-dopaminergic-neurons
#11
Denise Franz, Hervør Lykke Olsen, Oliver Klink, Jan Gimsa
Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated NaV and KV channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K(+) current (delayed KV) and rapidly inactivating A-type K(+) current (fast KV) were identified. Examination of the fast KV current with inhibitors yielded IC50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium)...
April 25, 2017: Scientific Data
https://www.readbyqxmd.com/read/28439401/long-non-coding-rna-malat1-contributes-to-cell-apoptosis-by-sponging-mir-124-in-parkinson-disease
#12
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/28437187/synergy-between-choroid-plexus-epithelial-cells-conditioned-medium-and-knockout-serum-replacement-converts-human-adipose-derived-stem-cells-to-dopamine-secreting-neurons
#13
Mahdi Eskandarian Boroujeni, Mossa Gardaneh, Mehrnoosh Hasan Shahriari, Abbas Aliaghaei, Sanaz Hasani
Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as non-mesodermal lineages including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of Choroid Plexus epithelial cells-conditioned medium (CPEC-CM) alone or cocktailed with knock-out serum (KS) to induce dopaminergic differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so selected media easily differentiated them into osteoblasts, chondrocytes and adipocytes...
March 2, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#14
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28432706/varied-pathological-and-therapeutic-response-effects-associated-with-chchd2-mutant-and-risk-variants
#15
Murni Tio, Rujing Wen, Yih Lin Lim, Zul Haikhel Bin Zukifli, Shaoping Xie, Patrick Ho, Zhidong Zhou, Tong-Wey Koh, Yi Zhao, Eng-King Tan
Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction which could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress and impairment in synaptic transmission...
April 21, 2017: Human Mutation
https://www.readbyqxmd.com/read/28431219/genetic-analysis-of-%C3%AE-synuclein-3-untranslated-region-and-its-corresponding-micrornas-in-relation-to-parkinson-s-compared-to-dementia-with-lewy-bodies
#16
Lidia Tagliafierro, Omolara-Chinue Glenn, Madison E Zamora, Thomas G Beach, Randy L Woltjer, Michael W Lutz, Ornit Chiba-Falek
INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time PCR to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants...
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28429275/tgf-%C3%AE-1-neuroprotection-via-inhibition-of-microglial-activation-in-a-rat-model-of-parkinson-s-disease
#17
Xiao Chen, Zhan Liu, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
Transforming growth factor (TGF)-β1 is a pleiotropic cytokine with immunosuppressive and anti-inflammatory properties. Recently we have shown that TGF-β1 pretreatment in vitro protects against 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neuronal loss that characterizes in Parkinson's disease (PD). Herein, we aimed to demonstrate that TGF-β1 administration in vivo after MPP(+) toxicity has neuroprotection that is achieved by a mediation of microglia. A rat model of PD was prepared by injecting MPP(+) unilaterally in the striatum...
April 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28427412/lack-of-interleukin-13-receptor-%C3%AE-1-delays-the-loss-of-dopaminergic-neurons-during-chronic-stress
#18
Simone Mori, Shuei Sugama, William Nguyen, Tatiana Michel, M Germana Sanna, Manuel Sanchez-Alavez, Rigo Cintron-Colon, Gianluca Moroncini, Yoshihiko Kakinuma, Pamela Maher, Bruno Conti
BACKGROUND: The majority of Parkinson's disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress...
April 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28426941/behavioral-deficits-and-neural-damage-of-caenorhabditis-elegans-induced-by-three-rare-earth-elements
#19
Tiantian Xu, Manke Zhang, Jiani Hu, Zihan Li, Taipu Wu, Jianing Bao, Siyu Wu, Lili Lei, Defu He
Rare earth elements (REEs) are widely used in industry, agriculture, medicine and daily life in recent years. However, environmental and health risks of REEs are still poorly understood. In this study, neurotoxicity of trichloride neodymium, praseodymium and scandium were evaluated using nematode Caenorhabditis elegans as the assay system. Median lethal concentrations (48 h) were 99.9, 157.2 and 106.4 mg/L for NdCl3, PrCl3 and ScCl3, respectively. Sublethal dose (10-30 mg/L) of these trichloride salts significantly inhibited body length of nematodes...
April 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28425631/restraint-stress-increases-prolactin-mediated-phosphorylation-of-signal-transducer-and-activator-of-transcription-5-in-the-hypothalamus-and-adrenal-cortex-in-the-male-mouse
#20
S E Kirk, T Y Xie, F J Steyn, D R Grattan, S J Bunn
Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the anterior pituitary. Its rate of secretion is primarily regulated by a negative feedback mechanism whereby prolactin stimulates the activity of the tuberoinfundibular dopaminergic (TIDA) neurons, increasing their release of dopamine which accesses the pituitary via the median eminence to suppress further prolactin secretion. In addition to its well established role in lactation, circulating prolactin is secreted in response to stress, although the mechanism by which this is achieved or its cellular targets are unknown...
April 20, 2017: Journal of Neuroendocrinology
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