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6-OHDA

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https://www.readbyqxmd.com/read/29346382/6-ohda-induced-dopaminergic-neurodegeneration-in-caenorhabditis-elegans-is-promoted-by-the-engulfment-pathway-and-inhibited-by-the-transthyretin-related-protein-ttr-33
#1
Sarah-Lena Offenburger, Xue Yan Ho, Theresa Tachie-Menson, Sean Coakley, Massimo A Hilliard, Anton Gartner
Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson's disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting Caenorhabditis elegans dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the transthyretin-related gene ttr-33. The only described C. elegans transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#2
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29329678/apelin-13-ameliorates-cognitive-impairments-in-6-hydroxydopamine-induced-substantia-nigra-lesion-in-rats
#3
Elham Haghparast, Saeed Esmaeili-Mahani, Mehdi Abbasnejad, Vahid Sheibani
Although Parkinson's disease (PD) is well known with its motor deficits, the patients often suffer from cognitive dysfunction. Apelin, as the endogenous ligand of the APJ receptor, is found in several brain regions such as substantia nigra and mesolimbic pathway. However, the role of apelin in cognition and cognitive disorders has not been fully clarified. In this study the effects of apelin-13 were investigated on cognitive disorders in rat Parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the substantia nigra...
January 5, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29327199/glycogen-synthase-kinase-3%C3%AE-regulates-equilibrium-between-neurogenesis-and-gliogenesis-in-rat-model-of-parkinson-s-disease-a-crosstalk-with-wnt-and-notch-signaling
#4
Sonu Singh, Akanksha Mishra, Sachi Bharti, Virendra Tiwari, Jitendra Singh, Parul, Shubha Shukla
Neurogenesis involves generation of functional newborn neurons from neural stem cells (NSCs). Insufficient formation or accelerated degeneration of newborn neurons may contribute to the severity of motor/nonmotor symptoms of Parkinson's disease (PD). However, the functional role of adult neurogenesis in PD is yet not explored and whether glycogen synthase kinase-3β (GSK-3β) affects multiple steps of adult neurogenesis in PD is still unknown. We investigated the possible underlying molecular mechanism of impaired adult neurogenesis associated with PD...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29305892/the-involvement-of-the-pathway-connecting-the-substantia-nigra-the-periaqueductal-gray-matter-and-the-retrotrapezoid-nucleus-in-breathing-control-in-a-rat-model-of-parkinson-s-disease
#5
Juliana C Lima, Luiz M Oliveira, Marina T Botelho, Thiago S Moreira, Ana C Takakura
Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6-OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions...
January 4, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29291419/neuroprotective-effect-of-olfactory-ensheathing-cells-co-transfected-with-nurr1-and-ngn2-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#6
Qingqing Liu, Qi Qin, Hongxue Sun, Di Zhong, Ran An, Yushuang Tian, Hongping Chen, Jing Jin, Haining Wang, Guozhong Li
AIMS: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. MATERIALS AND METHODS: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+-treated PC12 cells for 24h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected...
December 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/29289596/neuronal-activity-pattern-defects-in-the-striatum-in-awake-mouse-model-of-parkinson-s-disease
#7
Hui Chen, Huimeng Lei, Qunyuan Xu
Previous studies showed the loss of dopaminergic neurons directly leads to both changes in firing rate and neuronal synchrony in the striatum by pharmacogenetic approach, but physiological observation of striatal neurons in awake animal is rare up to now due to the limitation of recording methods. We use multichannel in vivo recording system, to record the activity pattern of both medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) in awake mouse model of Parkinson's disease (PD), created by injection of 6-hydroxyl-dopamine (6-OHDA) into dorsolateral striatum bilaterally and unilaterally...
December 29, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29286349/compressional-puffing-pretreatment-enhances-neuroprotective-effects-of-fucoidans-from-the-brown-seaweed-sargassum-hemiphyllum-on-6-hydroxydopamine-induced-apoptosis-in-sh-sy5y-cells
#8
Chun-Yung Huang, Chia-Hung Kuo, Po-Wei Chen
In this study, a compressional-puffing process (CPP) was used to pretreat Sargassum hemiphyllum (SH) and then fucoidan was extracted from SH by hot water. Three fucoidan extracts, namely SH1 (puffing at 0 kg/cm²); SH2 (puffing at 1.7 kg/cm²); and SH3 (puffing at 10.0 kg/cm²) were obtained, and their compositions and biological activities were evaluated. The results indicate that CPP increased the extraction yield, total sugar content, and molar ratios of sulfate/fucose of fucoidan and decreased molecular weight and impurities of fucoidan...
December 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29285938/novel-kunitz-like-peptides-discovered-in-the-zoanthid-palythoa-caribaeorum-through-transcriptome-sequencing
#9
Qiwen Liao, Shengnan Li, Shirley Weng In Siu, Binrui Yang, Chen Huang, Judy Yuet-Wa Chan, Jean-Étienne Morlighem, Clarence Tsun Ting Wong, Gandhi Radis-Baptista, Simon Ming-Yuen Lee
Palythoa caribaeorum (class Anthozoa) is a zoanthid that together jellyfishes, hydra, and sea anemones, which are venomous and predatory, belongs to the Phyllum Cnidaria. The distinguished feature in these marine animals is the cnidocytes in the body tissues, responsible for toxin production and injection that are used majorly for prey capture and defense. With exception for other anthozoans, the toxin cocktails of zoanthids have been scarcely studied and are poorly known. Here, based on the analysis of P. caribaeorum transcriptome, numerous predicted venom-featured polypeptides were identified, including allergens, neurotoxins, membrane-active and Kunitz-like peptides (PcKuz)...
December 29, 2017: Journal of Proteome Research
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
#10
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/29248613/high-frequency-stimulation-induces-ltd-of-ampa-receptor-mediated-postsynaptic-responses-and-ltp-of-synaptically-evoked-firing-in-the-dorsolateral-striatum
#11
Olga Skiteva, Ning Yao, Mona Nouhi, Karima Chergui
In the striatum, long term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are believed to underlie motor learning and are impaired in animal models of Parkinson's disease. High frequency stimulation (HFS) is often used to induce synaptic plasticity in the brain. In the striatum, the polarity of HFS-induced plasticity is influenced by the recording conditions, which can differ between various studies. Here, we examined the ability of HFS to induce synaptic plasticity in the dorsolateral striatum in the presence of extracellular Mg2+ ions, with no GABAA receptor blocker, and without membrane depolarization during HFS...
December 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29242978/animal-models-of-l-dopa-induced-dyskinesia-the-6-ohda-lesioned-rat-and-mouse
#12
REVIEW
Elisabetta Tronci, Veronica Francardo
Appearance of L-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor L-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9-10 years of L-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson's disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i...
December 14, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29241709/regulation-of-pleiotrophin-and-fyn-in-the-striatum-of-rats-undergoing-l-dopa-induced-dyskinesia
#13
Gimena Gomez, Mariano D Saborido, María A Bernardi, Oscar S Gershanik, Irene R Taravini, Juan E Ferrario
L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats...
December 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29240240/ultrasound-triggered-effects-of-the-microbubbles-coupled-to-gdnf-and-nurr1-loaded-pegylated-liposomes-in-a-rat-model-of-parkinson-s-disease
#14
Peijian Yue, Lin Gao, Xuejing Wang, Xuebing Ding, Junfang Teng
The purpose of this study was to investigate ultrasound-triggered effects of the glial cell line-derived neurotrophic factor (GDNF) + nuclear receptor-related factor 1 (Nurr1)-polyethylene glycol (PEG)ylated liposomes-coupled microbubbles (PLs-GDNF+Nurr1-MBs) on behavioral impairment and neuron loss in a rat model of Parkinson's disease (PD). The unloaded PEGylated liposomes-coupled microbubbles (PLs-MBs) were characterized for zeta potential, particle size, and concentration. 6-hydroxydopamine (6-OHDA) was used to establish the PD rat model...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29239973/involvement-of-adenosine-triphosphate-sensitive-potassium-channels-in-the-neuroprotective-activity-of-hydrogen-sulfide-in-the-6-hydroxydopamine-induced-animal-model-of-parkinson-s-disease
#15
Mohammad Reza Sarookhani, Hashem Haghdoost-Yazdi, Ali Sarbazi-Golezari, Arvin Babayan-Tazehkand, Nafiseh Rastgoo
Studies have shown that hydrogen sulfide (H2S) exerts a neuroprotective effect and may have a therapeutic value for treating neurodegenerative diseases including Parkinson's disease. However, little is known about the mechanisms underlying the neuroprotective activity of H2S in vivo. Here, we evaluated the effect of glibenclamide, an ATP-sensitive potassium channel blocker, on the neuroprotective activity of H2S in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease. 6-OHDA was administered by stereotaxic surgery into the medial forebrain bundle...
December 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29226687/validation-of-a-new-scoring-scale-for-behavioral-assessment-of-l-dopa-induced-dyskinesia-in-the-rat-a-new-tool-for-early-decision-making-in-drug-development
#16
Simon Loiodice, Anne-Sophie Denibaud, Wendy Deffains, Magali Alix, Pierre Montagne, Marine Seffals, Christophe Drieu La Rochelle
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated non-human primate (NHP) has been described as the most translatable model for experimental reproduction of L-dopa-induced dyskinesia (LID). However, from a drug discovery perspective, the risk associated with investment in this type of model is high due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is recommended for testing compounds but relies on onerous, and non-standard behavioral rating scales. We sought to develop a simplified and sensitive method aiming at assessing LID in the rat...
December 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29204750/protective-effects-of-fisetin-against-6-ohda-induced-apoptosis-by-activation-of-pi3k-akt-signaling-in-human-neuroblastoma-sh-sy5y-cells
#17
Ryoko Watanabe, Takumi Kurose, Yuta Morishige, Ko Fujimori
6-Hydroxydopamine (6-OHDA) induces the production of reactive oxygen species (ROS) that are associated with various neurodegenerative diseases such as Parkinson's disease. 3,3',4',7-Tetrahydroxyflavone (fisetin), a plant flavonoid has a variety of physiological effects such as antioxidant activity. In this study, we investigated the molecular mechanism of the neuroprotective effects of fisetin against 6-OHDA-induced cell death in human neuroblastoma SH-SY5Y cells. 6-OHDA-mediated cell toxicity was reduced in a fisetin concentration-dependent manner...
December 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29204298/treadmill-exercise-improves-motor-dysfunction-and-hyperactivity-of-the-corticostriatal-glutamatergic-pathway-in-rats-with-6-ohda-induced-parkinson-s-disease
#18
Wei Chen, Decai Qiao, Xiaoli Liu, Kaixuan Shi
Hyperactivity in the corticostriatal glutamatergic pathway (CGP) induces basal ganglia dysfunction, contributing to parkinsonian syndrome (PS). Physical exercise can improve PS. However, the effect of exercise on the CGP, and whether this pathway is involved in the improvement of PS, remains unclear. Parkinson's disease (PD) was induced in rats by 6-hydroxydopamine injection into the right medial forebrain bundle. Motor function was assessed using the cylinder test. Striatal neuron (SN) spontaneous and evoked firing activity was recorded, and the expression levels of Cav1...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29197517/dpi-289-a-novel-mixed-delta-opioid-agonist-mu-opioid-antagonist-dama-has-l-dopa-sparing-potential-in-parkinson-s-disease
#19
Tom H Johnston, Eboo Versi, Patrick A Howson, Paula Ravenscroft, Susan H Fox, Michael P Hill, Bruce E Reidenberg, Ronald Corey, Jonathan M Brotchie
L-DOPA-induced dyskinesia (LID) remains a significant problem in the management of Parkinson's disease (PD). In rodent and macaque models of PD, delta opioid receptor agonists have anti-parkinsonian actions while mu opioid antagonists can reduce the expression of LID. DPI-289 is a novel molecule with a unique combination of opioid receptor DAMA actions: delta agonist (Ki: 0.73 nM); mu antagonist (Ki: 12 nM). We demonstrated that DPI-289 has oral bioavailability and established its pharmacokinetic profile in both rat and primate...
November 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29195909/protective-effects-of-%C3%AE-mangostin-on-6-ohda-induced-toxicity-in-sh-sy5y-cells
#20
Yamaratee Jaisin, Piyanee Ratanachamnong, Chitraporn Kuanpradit, Watinee Khumpum, Sunit Suksamrarn
γ-Mangostin is a xanthone with hydroxyl groups that confer the substance-free radical scavenging effects. As opposed to the other more extensively studied mangostins, scarce research has been conducted on neuroprotective effects of γ-mangostin on models of Parkinson's disease (PD). Therefore, this investigation aimed to elucidate its antioxidant and neuroprotective effects on 6-OHDA-induced toxicity in SH-SY5Y cells. 6-OHDA treatment, an inducer of PD pathology in vitro studies, decreased cell viability and increased the level of intracellular ROS production...
November 28, 2017: Neuroscience Letters
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