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Parkinson's disease animal models

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https://www.readbyqxmd.com/read/29684508/methylene-blue-ameliorates-olfactory-dysfunction-and-motor-deficits-in-a-chronic-mptp-probenecid-mouse-model-of-parkinson-s-disease
#1
K C Biju, Robert C Evans, Kripa Shrestha, Daniel C B Carlisle, Jonathan Gelfond, Robert A Clark
Mitochondrial dysfunction and oxidative stress are very prominent and early features in Parkinson's disease (PD) and in animal models of PD. Thus, antioxidant therapy for PD has been proposed, but in clinical trials such strategies have met with very limited success. Methylene blue (MB), a small-molecule synthetic heterocyclic organic compound that acts as a renewable electron cycler in the mitochondrial electron transport chain, manifesting robust antioxidant and cell energetics-enhancing properties, has recently been shown to have significant beneficial effects in reducing nigrostriatal dopaminergic loss and motor impairment in acute toxin models of PD...
April 20, 2018: Neuroscience
https://www.readbyqxmd.com/read/29683090/effects-of-aging-in-the-striatum-and-substantia-nigra-of-a-parkinson-s-disease-animal-model
#2
Rodrigo Portes Ureshino, Angelica Jardim Costa, Adolfo Garcia Erustes, Gustavo José da Silva Pereira, Rita Sinigaglia-Coimbra, Soraya Soubhi Smaili
Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological models, but due to the limitations of the animal models, particularly in aged animals, the results are difficult to interpret. In this work, we investigated neurodegeneration induced by rotenone, as a pharmacological model of Parkinson's disease, in both young and aged Wistar rats...
April 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29681024/extracellular-alpha-synuclein-oligomers-induce-parkin-s-nitrosylation-relevance-to-sporadic-parkinson-s-disease-etiopathology
#3
Anna Wilkaniec, Anna M Lenkiewicz, Grzegorz A Czapski, Henryk M Jęśko, Wojciech Hilgier, Robert Brodzik, Magdalena Gąssowska-Dobrowolska, Carsten Culmsee, Agata Adamczyk
α-Synuclein (ASN) and parkin, a multifunctional E3 ubiquitin ligase, are two proteins that are associated with the pathophysiology of Parkinson's disease (PD). Excessive release of ASN, its oligomerization, aggregation, and deposition in the cytoplasm contribute to neuronal injury and cell death through oxidative-nitrosative stress induction, mitochondrial impairment, and synaptic dysfunction. In contrast, overexpression of parkin provides protection against cellular stresses and prevents dopaminergic neural cell loss in several animal models of PD...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29681010/impaired-tissue-barriers-as-potential-therapeutic-targets-for-parkinson-s-disease-and-amyotrophic-lateral-sclerosis
#4
REVIEW
Xin Fang
The blood-brain barrier and the intestinal barrier show signs of disruption in patients with idiopathic Parkinson's disease (PD) and animal models of nigrostriatal degeneration, and likewise in amyotrophic lateral sclerosis (ALS) models. A substantial body of evidence shows that defects in epithelial membrane barriers, both in the gut and within the cerebral vasculature, can result in increased vulnerability of tissues to external factors potentially participating in the pathogenesis of PD and ALS. As such, restoration of tissue barriers may prove to be a novel therapeutic target in neurodegenerative disease...
April 22, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29680709/parkinson-s-disease-like-burst-firing-activity-in-subthalamic-nucleus-induced-by-aav-%C3%AE-synuclein-is-normalized-by-lrrk2-modulation
#5
Michael Aagaard Andersen, Kenneth Vielsted Christensen, Lassina Badolo, Garrick Paul Smith, Ross Jeggo, Poul Henning Jensen, Kathrine Just Andersen, Florence Sotty
Parkinson's disease (PD) affects motor function through degenerative processes and synaptic transmission impairments in the basal ganglia. None of the treatments available delays or stops the progression of the disease. While α-synuclein pathological accumulation represents a hallmark of the disease in its idiopathic form, leucine rich repeat kinase 2 (LRRK2) is genetically associated with familial and sporadic forms of PD. The genetic information suggests that LRRK2 kinase activity plays a role in the pathogenesis of the disease...
April 19, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29676481/high-mobility-group-box-1-in-parkinson-s-disease-from-pathogenesis-to-therapeutic-approaches
#6
REVIEW
Efthalia Angelopoulou, Christina Piperi, Athanasios G Papavassiliou
Parkinson's disease (PD) presents the second most common neurodegenerative disorder with largely unknown pathogenesis and inefficient therapeutic management. Accumulating data indicate that neuroinflammation, autophagy impairment, α-synuclein aggregation and mitochondrial dysfunction may contribute to PD onset; however the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that High-mobility group box 1 (HMGB1), a DNA-binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role in PD pathogenesis...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29676205/effects-of-peptidyl-prolyl-isomerase-1-depletion-in-animal-models-of-prion-diseases
#7
Giuseppe Legname, Tommaso Virgilio, Edoardo Bistaffa, Chiara Maria Giulia De Luca, Marcella Catania, Paola Zago, Elisa Isopi, Ilaria Campagnani, Fabrizio Tagliavini, Giorgio Giaccone, Fabio Moda
Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1+/+ ), hemizygous (Pin1+/- ) or knock-out (Pin1-/- ) background for Pin1 were experimentally infected with RML prions...
April 20, 2018: Prion
https://www.readbyqxmd.com/read/29675823/impact-of-neurodegenerative-diseases-on-drug-binding-to-brain-tissues-from-animal-models-to-human-samples
#8
Ana Ugarte, David Corbacho, María S Aymerich, Ana García-Osta, Mar Cuadrado-Tejedor, Julen Oyarzabal
Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD)...
April 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29673238/association-of-exercise-induced-autophagy-upregulation-and-apoptosis-suppression-with-neuroprotection-against-pharmacologically-induced-parkinson-s-disease
#9
Yong Chul Jang, Dong Joo Hwang, Jung Hoon Koo, Hyun Seob Um, Nam Hee Lee, Dong Cheol Yeom, Youngil Lee, Joon Yong Cho
PURPOSE: We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD). METHODS: PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10)...
March 30, 2018: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/29672668/distinct-effects-of-apathy-and-dopamine-on-effort-based-decision-making-in-parkinson-s-disease
#10
Campbell Le Heron, Olivia Plant, Sanjay Manohar, Yuen-Siang Ang, Matthew Jackson, Graham Lennox, Michele T Hu, Masud Husain
Effort-based decision-making is a cognitive process crucial to normal motivated behaviour. Apathy is a common and disabling complication of Parkinson's disease, but its aetiology remains unclear. Intriguingly, the neural substrates associated with apathy also subserve effort-based decision-making in animal models and humans. Furthermore, the dopaminergic system plays a core role in motivating effortful behaviour for reward, and its dysfunction has been proposed to play a crucial role in the aetiology of apathy in Parkinson's disease...
April 17, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29667931/ave0991-a-nonpeptide-analogue-of-ang-1-7-attenuates-aging-related-neuroinflammation
#11
Teng Jiang, Liu-Jun Xue, Yang Yang, Qing-Guang Wang, Xiao Xue, Zhou Ou, Qing Gao, Jian-Quan Shi, Liang Wu, Ying-Dong Zhang
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7)...
April 17, 2018: Aging
https://www.readbyqxmd.com/read/29667128/epigallocatechin-3-gallate-protects-and-prevents-paraquat-induced-oxidative-stress-and-neurodegeneration-in-knockdown-dj-1-%C3%AE-drosophila-melanogaster
#12
Daniel A Martinez-Perez, Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
Epigallocatechin-3-gallate (EGCG) is a polyhydroxyphenol constituent of green tea (e.g., Camellia sinensis) with known antioxidant properties. Due to these properties, others have proposed it as a potential therapeutic agent for the treatment of Parkinson's disease (PD). Previously, we demonstrated that EGCG prolonged the lifespan and locomotor activity in wild-type Canton-S flies exposed to the neurotoxicant paraquat (PQ), suggesting neuroprotective properties. Both gene mutations and environmental neurotoxicants (e...
April 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29665491/methamphetamine-use-and-future-risk-for-parkinson-s-disease-evidence-and-clinical-implications
#13
REVIEW
Julia M Lappin, Shane Darke, Michael Farrell
BACKGROUND: Methamphetamine use has been posited to be a risk factor for the development of Parkinson's disease (PD) and parkinsonism. The clinical implications of a potential association between methamphetamine use and PD are considered. METHODS: A review of methamphetamine and PD and parkinsonism was conducted, including evidence from animal models, clinical and population studies. RESULTS: There is biological plausibility to a link between methamphetamine use and PD...
April 10, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29662431/the-neuroprotective-effects-of-thymoquinone-a-review
#14
Tahereh Farkhondeh, Saeed Samarghandian, Ali Mohammad Pourbagher Shahri, Fariborz Samini
Thymoquinone (TQ), one of the main components active of Nigella sativa , exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on...
April 2018: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/29661608/modafinil-alleviates-levodopa-induced-excessive-nighttime-sleepiness-and-restores-monoaminergic-systems-in-a-nocturnal-animal-model-of-parkinson-s-disease
#15
Rina Ando, Mohammed Emamussalehin Choudhury, Yuki Yamanishi, Win Thiri Kyaw, Madoka Kubo, Mariko Kannou, Noriko Nishikawa, Junya Tanaka, Masahiro Nomoto, Masahiro Nagai
Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG analyses of whole day recordings revealed that modafinil reduce ENS of this nocturnal PD models with levodopa medications...
March 31, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29653138/neuroprotective-action-of-4-hydroxyisophthalic-acid-against-paraquat-induced-motor-impairment-involves-amelioration-of-mitochondrial-damage-and-neurodegeneration-in-drosophila
#16
Niveditha S, T Shivanandappa
Neurodegenerative disorders including Parkinson's disease (PD) are believed to be caused by oxidative stress and mitochondrial dysfunction. Exposure to environmental agents such as pesticides has been implicated in the etiology of sporadic PD. Paraquat (PQ), a widely used herbicide, induces PD symptoms in laboratory animals including Drosophila. PQ acts as a free radical generator and induces oxidative damage, which is implicated in neuronal cell death. Drosophila model of PQ-induced PD offers a convenient tool for mechanistic studies and, to assess the neuroprotective potential of natural antioxidants...
April 10, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29651747/tauroursodeoxycholic-acid-improves-motor-symptoms-in-a-mouse-model-of-parkinson-s-disease
#17
Alexandra Isabel Rosa, Sara Duarte-Silva, Anabela Silva-Fernandes, Maria João Nunes, Andreia Neves Carvalho, Elsa Rodrigues, Maria João Gama, Cecília Maria Pereira Rodrigues, Patrícia Maciel, Margarida Castro-Caldas
Parkinson's disease (PD) is characterized by severe motor symptoms, and currently there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD; however, its effect in PD motor symptoms has never been addressed. In the present work, an extensive behavior analysis was performed to better characterize the MPTP model of PD and to evaluate the effects of TUDCA in the prevention/improvement of mice phenotype...
April 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29649621/astrocyte-specific-dj-1-overexpression-protects-against-rotenone-induced-neurotoxicity-in-a-rat-model-of-parkinson-s-disease
#18
Briana R De Miranda, Emily M Rocha, Qing Bai, Amina El Ayadi, David Hinkle, Edward A Burton, J Timothy Greenamyre
DJ-1 is a redox-sensitive protein with several putative functions important in mitochondrial physiology, protein transcription, proteasome regulation, and chaperone activity. High levels of DJ-1 immunoreactivity are reported in astrocytes surrounding pathology associated with idiopathic Parkinson's disease, possibly reflecting the glial response to oxidative damage. Previous studies showed that astrocytic over-expression of DJ-1 in vitro prevented oxidative stress and mitochondrial dysfunction in primary neurons...
April 9, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29649433/repurposing-sex-steroids-and-related-drugs-as-potential-treatment-for-parkinson-s-disease
#19
REVIEW
Mélanie Bourque, Marc Morissette, Thérèse Di Paolo
Parkinson's disease (PD) is a neurodegenerative disorder for which a greater prevalence and incidence is described in men. This suggests a protective effect of sex hormones in the brain. Therefore, steroids and drugs to treat endocrine conditions could have additional application for PD. Here, we review the protective effect of sex hormones, particularly estrogens, progesterone, androgens and dehydroepiandrosterone, in animal models of PD and also in human studies. Data also support that drugs affecting estrogen neurotransmission such as selective estrogen receptor modulators or affecting steroid metabolism with 5α-reductase inhibitors could be repositioned for treatment of PD...
April 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29628879/dopamine-effort-based-choice-and-behavioral-economics-basic-and-translational-research
#20
REVIEW
John D Salamone, Merce Correa, Jen-Hau Yang, Renee Rotolo, Rose Presby
Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA) system and other brain circuits, are involved in regulating effort-related aspects of motivation...
2018: Frontiers in Behavioral Neuroscience
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