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https://www.readbyqxmd.com/read/28822080/soluble-epoxide-hydrolase-inhibition-attenuates-mptp-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-involvement-of-%C3%AE-synuclein-aggregation-and-er-stress
#1
Hui-Ju Huang, Yi-Ting Wang, Hui-Ching Lin, Yi-Hsuan Lee, Anya Maan-Yuh Lin
Soluble epoxide hydrolase (sEH) is widely expressed in the mammalian brain and possesses dual enzymatic activities, including C-terminal epoxide hydrolase (C-EH) which degrades epoxyeicosatrienoic acid (EET), a beneficial arachidonic acid metabolite. In the present study, the neuroprotective effect of sEH inhibition on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using genetic and pharmacological approaches. MPTP (15 mg/kg) was intraperitoneally injected in sEH knockout (KO) mice and C57BL/6J mice as wild-type (WT) mice...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28811225/alpha-synuclein-ferrireductase-activity-is-detectible-in-vivo-is-altered-in-parkinson-s-disease-and-increases-the-neurotoxicity-of-dopal
#2
Jennifer S McDowall, Ioanna Ntai, Kevin C Honeychurch, John P Hart, Philippe Colin, Bernard L Schneider, David R Brown
The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be determined in vivo...
August 12, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28790019/neuronal-firing-activity-in-the-basal-ganglia-after-striatal-transplantation-of-dopamine-neurons-in-hemiparkinsonian-rats
#3
Regina Rumpel, Mesbah Alam, Lisa M Schwarz, Andreas Ratzka, Xingxing Jin, Joachim K Krauss, Claudia Grothe, Kerstin Schwabe
The loss of nigral dopaminergic neurons and the resulting dopamine (DA) depletion in the striatum (STR) lead to altered neuronal activity and enhanced beta activity in various regions of the basal ganglia (BG) motor loop in patients with Parkinson's disease and in rodents in the 6-hydroxydopamine (6-OHDA)-lesioned rat model. Intrastriatal DA graft implantation has been shown to re-innervate the host brain and restore DA input. Here, DA cell grafts were implanted into the STR of 6-OHDA-lesioned rats and the effect on neuronal activity under urethane anesthesia (1...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28770670/potential-repositioning-of-exemestane-as-a-neuroprotective-agent-for-parkinson-s-disease
#4
Hyo Jin Son, Se Hee Han, Ji Ae Lee, Eun Jung Shin, Onyou Hwang
Parkinson's disease (PD) is a neurodegenerative disorder characterised by selective degeneration of the nigral dopaminergic neurons, and neuroinflammation and oxidative stress are believed to be involved in its pathogenesis. In the present study, we provide data that the synthetic steroid exemestane, which is currently being used to treat breast cancer, may be useful for PD therapy. In BV-2 microglial cells, exemestane activated the transcription factor Nrf2 and induced expression of the Nrf2-dependent genes that encode the antioxidant enzymes NAD(P)H: quinone oxidoreductase 1, haem oxygenase-1, and glutamylcysteine ligase...
June 2017: Free Radical Research
https://www.readbyqxmd.com/read/28764908/neuroprotective-effects-of-lentivirus-mediated-cystathionine-beta-synthase-overexpression-against-6-ohda-induced-parkinson-s-disease-rats
#5
Yin Weilan, Yin Weiguo, Huang Baisheng, Wu Lixiang
Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with α-synuclein protein accumulation in these neurons. Hydrogen sulfide (H2S) plays an important role in the nervous system. Studies have shown that H2S has a protective effect on PD. However, as a kind of gas molecules, H2S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H2S in the brain...
July 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28743955/early-synaptic-dysfunction-induced-by-%C3%AE-synuclein-in-a-rat-model-of-parkinson-s-disease
#6
Jenny-Ann Phan, Kathrine Stokholm, Justyna Zareba-Paslawska, Steen Jakobsen, Kim Vang, Albert Gjedde, Anne M Landau, Marina Romero-Ramos
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [(11)C]dihydrotetrabenazine (DTBZ)...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738061/magnetic-resonance-imaging-and-tensor-based-morphometry-in-the-mptp-non-human-primate-model-of-parkinson-s-disease
#7
Michel Modo, William R Crum, Madeline Gerwig, Anthony C Vernon, Priya Patel, Michael J Jackson, Sarah Rose, Peter Jenner, Mahmoud M Iravani
Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD...
2017: PloS One
https://www.readbyqxmd.com/read/28676738/the-multiple-correspondence-analysis-method-and-brain-functional-connectivity-its-application-to-the-study-of-the-non-linear-relationships-of-motor-cortex-and-basal-ganglia
#8
Clara Rodriguez-Sabate, Ingrid Morales, Alberto Sanchez, Manuel Rodriguez
The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28676095/toll-like-receptor-4-stimulation-with-monophosphoryl-lipid-a-ameliorates-motor-deficits-and-nigral-neurodegeneration-triggered-by-extraneuronal-%C3%AE-synucleinopathy
#9
Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K Wenning, Nadia Stefanova
BACKGROUND: Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be a natural mechanism to improve the clearance of α-syn...
July 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28673739/sirtuin-3-rescues-neurons-through-the-stabilisation-of-mitochondrial-biogenetics-in-the-virally-expressing-mutant-%C3%AE-synuclein-rat-model-of-parkinsonism
#10
Jacqueline A Gleave, Lindsay R Arathoon, Dennison Trinh, Kristin E Lizal, Nicolas Giguère, James H M Barber, Zainab Najarali, M Hassan Khan, Sherri L Thiele, Mahin S Semmen, James B Koprich, Jonathan M Brotchie, James H Eubanks, Louis-Eric Trudeau, Joanne E Nash
Parkinson's disease (PD) is a neurodegenerative movement disorder, which affects approximately 1-2% of the population over 60years of age. Current treatments for PD are symptomatic, and the pathology of the disease continues to progresses over time until palliative care is required. Mitochondria are key players in the pathology of PD. Genetic and post mortem studies have shown a large number of mitochondrial abnormalities in the substantia nigra pars compacta (SNc) of the parkinsonian brain. Furthermore, physiologically, mitochondria of nigral neurons are constantly under unusually high levels of metabolic stress because of the excitatory properties and architecture of these neurons...
July 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28672025/interleukin-6-regulates-iron-related-proteins-through-c-jun-n-terminal-kinase-activation-in-bv2-microglial-cell-lines
#11
Shida Zhou, Xinxing Du, Junxia Xie, Jun Wang
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) and subsequent DA depletion in the striatum. Microglia activation and nigral iron accumulation play important roles in the pathogenesis of PD. Activated microglia show increased iron deposits. However, the relationship between microglia activation and iron accumulation remains unclear. In the present study, we aimed to determine how iron levels affect interleukin-6 (IL-6) synthesis, and the effect of IL-6 on cellular iron metabolism in BV2 microglial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28671143/substantia-nigra-neuromelanin-as-an-imaging-biomarker-of-disease-progression-in-parkinson-s-disease
#12
Margherita Fabbri, Sofia Reimão, Miguel Carvalho, Rita G Nunes, Daisy Abreu, Leonor Correia Guedes, Raquel Bouça, Patricia P Lobo, Catarina Godinho, Miguel Coelho, Nilza C Gonçalves, Mario Miguel Rosa, Angelo Antonini, Joaquim J Ferreira
BACKGROUND: A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE: to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28659791/pentazocine-protects-sn4741-cells-against-mpp-induced-cell-damage-via-up-regulation-of-the-canonical-wnt-%C3%AE-catenin-signaling-pathway
#13
Jiancai Wang, Jintao Gu, Hao Wu, Gang Zhu, Dayun Feng, Yuqian Li, Wei Guo, Keyong Tian, Guodong Gao, Li Gao
The Wnt/β-catenin signaling pathway has been linked to many neurodegenerative diseases including Parkinson's disease (PD). A glycoprotein named Dickkopf-1 (Dkk1) can combine with the receptor complex on cell membrane to inhibit Wnt/β-catenin signaling. Opioids, a series of compounds including morphine, fentanyl and pentazocine, have been reported to contribute to the up-regulation of Wnt/β-catenin signaling. Naloxone is an antagonist that has been used as an antidote to opioids through mu-opioid receptor...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28659169/the-novel-compound-pbt434-prevents-iron-mediated-neurodegeneration-and-alpha-synuclein-toxicity-in-multiple-models-of-parkinson-s-disease
#14
David I Finkelstein, Jessica L Billings, Paul A Adlard, Scott Ayton, Amelia Sedjahtera, Colin L Masters, Simon Wilkins, David M Shackleford, Susan A Charman, Wojciech Bal, Izabela A Zawisza, Ewa Kurowska, Andrew L Gundlach, Sheri Ma, Ashley I Bush, Dominic J Hare, Philip A Doble, Simon Crawford, Elisabeth Cl Gautier, Jack Parsons, Penny Huggins, Kevin J Barnham, Robert A Cherny
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions...
June 28, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28633499/lateralized-basal-ganglia-vulnerability-to-pesticide-exposure-in-asymptomatic-agricultural-workers
#15
Mechelle M Lewis, Nicholas W Sterling, Guangwei Du, Eun-Young Lee, Grace Shyu, Michael Goldenberg, Thomas Allen, Christy Stetter, Lan Kong, Shedra Amy Snipes, Byron C Jones, Honglei Chen, Richard B Mailman, Xuemei Huang
Background: Pesticide exposure is linked to Parkinson's disease (PD), a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticide-exposed agricultural workers (AW) have nigral diffusion tensor (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28631520/striatal-changes-underlie-mpep-mediated-suppression-of-the-acquisition-and-expression-of-pramipexole-induced-place-preference-in-an-alpha-synuclein-rat-model-of-parkinson-s-disease
#16
Simon Loiodice, Portia McGhan, Vitalina Gryshkova, Renaud Fleurance, David Dardou, Aziz Hafidi, Andre Nogueira da Costa, Franck Durif
Impulsive-compulsive disorders in Parkinson's disease patients have been described as behavioural or substance addictions including pathological gambling or compulsive medication use of dopamine replacement therapy. A substantial gap remains in the understanding of these disorders. We previously demonstrated that the rewarding effect of the D2/D3 agonist pramipexole was enhanced after repeated exposure to L-dopa and alpha-synuclein mediated dopaminergic nigral loss with specific transcriptional signatures suggesting a key involvement of the glutamatergic pathway...
June 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28617379/-immunohistochemical-characteristics-of-the-substantia-nigra-neurons-of-the-human
#17
D E Korzhevskii, I P Grigor'ev, E G Sukhorukova, V V Gusel'nikova
AIM: To determine the cytochemical characteristics of unchanged neurons of the human substantia nigra using a wide range of immunocytochemical markers some of which (glutamate decarboxylase-65, PGP 9.5, non-phosphorylated neurofilament proteins, alpa-tubulin) have never been used for study of human dopaminergic neurons. MATERIAL AND METHODS: Fragments of human midbrain (17 men and women, aged from 28 to 78 years) from the archives of the Department of General and Specific Morphology of the Institute of Experimental Medicine were used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28597409/progression-and-persistence-of-neurotoxicity-induced-by-mdma-in-dopaminergic-regions-of-the-mouse-brain-and-association-with-noradrenergic-gabaergic-and-serotonergic-damage
#18
Giulia Costa, Micaela Morelli, Nicola Simola
The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to characterize how the number of administrations influenced the severity of MDMA-induced dopaminergic damage and to describe the localization and persistence of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we investigated whether dopaminergic damage was associated with noradrenergic, GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin transporter (SERT)...
June 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28595911/manganese-exposure-exacerbates-progressive-motor-deficits-and-neurodegeneration-in-the-mitopark-mouse-model-of-parkinson-s-disease-relevance-to-gene-and-environment-interactions-in-metal-neurotoxicity
#19
Monica R Langley, Shivani Ghaisas, Muhammet Ay, Jie Luo, Bharathi N Palanisamy, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Parkinson's disease (PD) is now recognized as a neurodegenerative condition caused by a complex interplay of genetic and environmental influences. Chronic manganese (Mn) exposure has been implicated in the development of PD. Since mitochondrial dysfunction is associated with PD pathology as well as Mn neurotoxicity, we investigated whether Mn exposure augments mitochondrial dysfunction and neurodegeneration in the nigrostriatal dopaminergic system using a newly available mitochondrially defective transgenic mouse model of PD, the MitoPark mouse...
June 19, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28580639/mesenchymal-stem-cells-stabilize-axonal-transports-for-autophagic-clearance-of-%C3%AE-synuclein-in-parkinsonian-models
#20
Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In this study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice...
August 2017: Stem Cells
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