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https://www.readbyqxmd.com/read/28224980/alpha-synuclein-prevents-the-formation-of-spherical-mitochondria-and-apoptosis-under-oxidative-stress
#1
Stefanie Menges, Georgia Minakaki, Patrick M Schaefer, Holger Meixner, Iryna Prots, Ursula Schlötzer-Schrehardt, Kristina Friedland, Beate Winner, Tiago F Outeiro, Konstanze F Winklhofer, Christine A F von Arnim, Wei Xiang, Jürgen Winkler, Jochen Klucken
Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed "mitospheres"...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224479/modulation-of-arts-and-xiap-by-parkin-is-associated-with-carnosic-acid-protects-sh-sy5y-cells-against-6-hydroxydopamine-induced-apoptosis
#2
Ru-Huei Fu, Li-Chun Huang, Chia-Yuan Lin, Chia-Wen Tsai
The mediation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) and X-liked inhibitor of apoptosis protein (XIAP) by parkin plays a critical role in preventing Parkinson's disease. We studied whether carnosic acid (CA) could prevent 6-hydroxydopamine (6-OHDA)-induced apoptosis by modulating ARTS and XIAP through parkin in SH-SY5Y cells. In cells treated with 6-OHDA, the protein expression of ARTS is increased and XIAP is decreased. Pretreatment of cells with CA reversed these effects. Moreover, CA attenuated the activation of caspase 9 and caspase 7 by 6-OHDA...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#3
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28223037/asymmetric-dopaminergic-degeneration-and-levodopa-alter-functional-corticostriatal-connectivity-bilaterally-in-experimental-parkinsonism
#4
Cyril Monnot, Xiaoqun Zhang, Sahar Nikkhou-Aski, Peter Damberg, Per Svenningsson
Asymmetric dopamine loss is commonly found in early Parkinson's disease (PD), but its effects on functional networks have been difficult to delineate in PD patients because of variations in age, disease duration and therapy. Here we used unilateral 6-hydroxydopamine-lesioned (6-OHDA) rats and controls and treated them with a single intraperitoneal injection of levodopa (L-DOPA) before performing diffusion weighted MRI and resting state functional MRI (rs-fMRI). In accordance with a neurodegeneration of the nigrostriatal dopaminergic pathway, diffusion tensor imaging showed increased radial diffusivity and decreased fractional anisotropy in the lesioned substantia nigra...
February 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28221817/neuroprotective-effect-of-omega-3-polyunsaturated-fatty-acids-in-the-6-ohda-model-of-parkinson-s-disease-is-mediated-by-a-reduction-of-inducible-nitric-oxide-synthase
#5
Marco Aurélio Mori, Ana Marcia Delattre, Bruno Carabelli, Claudia Pudell, Mariza Bortolanza, Pedro Vinícius Staziaki, Jesuí Vergilio Visentainer, Paula Fernandes Montanher, Elaine A Del Bel, Anete Curte Ferraz
OBJECTIVE: Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons...
February 21, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28221082/partial-lesion-of-the-nigrostriatal-dopamine-pathway-in-rats-impairs-egocentric-learning-but-not-spatial-learning-or-behavioral-flexibility
#6
Katharine M Seip-Cammack, James J Young, Megan E Young, Matthew L Shapiro
Degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD) causes motor dysfunction and cognitive impairment, but the etiology of the cognitive deficits remains unclear. The present study investigated the behavioral effects of partial lesions of the nigrostriatal dopamine (DA) pathway. Rats received bilateral infusions of either 6-hydroxydopamine (6-OHDA) or vehicle into the dorsolateral striatum and were tested in spatial and procedural learning tasks. Compared with intact rats, DA-depleted rats were impaired when the first task they learned required egocentric responses...
February 20, 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28216584/effects-of-postnatal-enriched-environment-in-a-model-of-parkinson-s-disease-in-adult-rats
#7
Adel Jungling, Dora Reglodi, Zsofia Nozomi Karadi, Gabor Horvath, Jozsef Farkas, Balazs Gaszner, Andrea Tamas
Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28210976/regenerative-medicine-for-parkinson-s-disease-using-differentiated-nerve-cells-derived-from-human-buccal-fat-pad-stem-cells
#8
Haruka Takahashi, Hiroshi Ishikawa, Akira Tanaka
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks...
February 16, 2017: Human Cell
https://www.readbyqxmd.com/read/28203480/a-novel-immunosuppressor-5r-5-hydroxytriptolide-alleviates-movement-disorder-and-neuroinflammation-in-a-6-ohda-hemiparkinsonian-rat-model
#9
Ruijun Su, Min Sun, Wei Wang, Jianliang Zhang, Li Zhang, Junli Zhen, Yanjing Qian, Yan Zheng, Xiaomin Wang
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Promising therapies for PD still need to be explored. Immune dysfunction has been found to be involved in PD pathogenesis. Here, a novel immunosuppressor, (5R)-5-hydroxytriptolide (LLDT8), was used to treat 6-hydroxydopamine (6-OHDA)-induced hemiparkinson rats. We found that oral administration of LLDT8 significantly alleviated apomorphine-induced rotations at a dose of 125 µg/kg, and improved performance in cylinder and rotarod tests at a lower dose of 31...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28199883/acetyl-l-carnitine-protects-dopaminergic-nigrostriatal-pathway-in-6-hydroxydopamine-induced-model-of-parkinson-s-disease-in-the-rat
#10
Siamak Afshin-Majd, Keyhan Bashiri, Zahra Kiasalari, Tourandokht Baluchnejadmojarad, Reza Sedaghat, Mehrdad Roghani
Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms...
February 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28194885/in-vivo-bioluminescence-imaging-of-neurogenesis-the-role-of-the-blood-brain-barrier-in-an-experimental-model-of-parkinson-s-disease
#11
Inga B Fricke, Sonja Schelhaas, Bastian Zinnhardt, Thomas Viel, Sven Hermann, Sébastien Couillard-Després, Andreas H Jacobs
Bioluminescence imaging in transgenic mice expressing firefly luciferase in Doublecortin(+) (Dcx) neuroblasts might serve as a powerful tool to study the role of neurogenesis in models of brain injury and neurodegeneration using non-invasive, longitudinal in vivo imaging. Therefore, we aimed to use BLI in B6(Cg)-Tyrc-2J/J Dcx-Luc (Doublecortin-Luciferase, Dcx-Luc) mice to investigate its suitability to assess neurogenesis in a unilateral injection model of Parkinson's disease. We further aimed to assess the blood brain barrier leakage associated with the intranigral 6-OHDA injection to evaluate its impact on substrate delivery and bioluminescence signal intensity...
February 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28191785/impact-of-the-secretome-of-human-mesenchymal-stem-cells-on-brain-structure-and-animal-behavior-in-a-rat-model-of-parkinson-s-disease
#12
Fábio G Teixeira, Miguel M Carvalho, Krishna M Panchalingam, Ana J Rodrigues, Bárbara Mendes-Pinheiro, Sandra Anjo, Bruno Manadas, Leo A Behie, Nuno Sousa, António J Salgado
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182766/cd24-expression-does-not-affect-dopamine-neuronal-survival-in-a-mouse-model-of-parkinson-s-disease
#13
Simon R W Stott, Shaista Hayat, Tom Carnwath, Shaady Garas, Jonathan P Sleeman, Roger A Barker
Parkinson's disease (PD) is a progressive neurodegenerative condition that is characterised by the loss of specific populations of neurons in the brain. The mechanisms underlying this selective cell death are unknown but by using laser capture microdissection, the glycoprotein, CD24 has been identified as a potential marker of the populations of cells that are affected in PD. Using in situ hybridization and immunohistochemistry on sections of mouse brain, we confirmed that CD24 is robustly expressed by many of these subsets of cells...
2017: PloS One
https://www.readbyqxmd.com/read/28178069/montelukast-treatment-protects-nigral-dopaminergic-neurons-against-microglial-activation-in-the-6-hydroxydopamine-mouse-model-of-parkinson-s-disease
#14
Hannah Jang, Sehwan Kim, Jae Man Lee, Yong-Seok Oh, Sang Myun Park, Sang Ryong Kim
Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions...
February 7, 2017: Neuroreport
https://www.readbyqxmd.com/read/28176408/hippocampal-release-of-dopamine-and-norepinephrine-encodes-novel-contextual-information
#15
Perla Moreno-Castilla, Rodrigo Pérez-Ortega, Valeria Violante-Soria, Israela Balderas, Federico Bermúdez-Rattoni
The detection and processing of novel information encountered in our environment is crucial for proper adaptive behavior and learning. Hippocampus is a prime structure for novelty detection that receives high-level inputs including context information. It is of our interest to understand the mechanisms by which the hippocampus processes contextual information. For this, we performed in vivo microdyalisis in order to monitor extracellular changes in neurotransmitter levels during Object Location Memory (OLM), a behavioral protocol developed to evaluate contextual information processing in recognition memory...
February 8, 2017: Hippocampus
https://www.readbyqxmd.com/read/28167258/protective-effect-of-nrf2-are-activator-isolated-from-green-perilla-leaves-on-dopaminergic-neuronal-loss-in-a-parkinson-s-disease-model
#16
Yuta Masaki, Yasuhiko Izumi, Atsuko Matsumura, Akinori Akaike, Toshiaki Kume
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN), and oxidative stress is thought to contribute to the pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which is a cellular defense system against oxidative stress, is a promising target for therapeutics aimed at reducing neuronal death in PD. Previously, we have isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla leaves as an activator of the Nrf2-ARE pathway...
February 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28157651/sesamin-imparts-neuroprotection-against-intrastriatal-6-hydroxydopamine-toxicity-by-inhibition-of-astroglial-activation-apoptosis-and-oxidative-stress
#17
Tourandokht Baluchnejadmojarad, Monireh Mansouri, Jamileh Ghalami, Zahra Mokhtari, Mehrdad Roghani
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry...
January 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28157650/urb597-reduces-biochemical-behavioral-and-morphological-alterations-in-two-neurotoxic-models-in-rats
#18
Marisol Maya-López, Hipolito A Ruiz-Contreras, María de Jesús Negrete-Ruíz, Julián Elías Martínez-Sánchez, Juan Benítez-Valenzuela, Ana Laura Colín-González, Juana Villeda-Hernández, Laura Sánchez-Chapul, Carmen Parra-Cid, Edgar Rangel-López, Abel Santamaría
BACKGROUND: URB597 is a compound largely linked to the inhibition of fatty acid amide hydrolase (FAAH), an enzyme responsible for the metabolic degradation of the endocannabinoid anandamide (AEA). Despite this pharmacological property accounts for its modulatory profile demonstrated in some neurotoxic paradigms, the possible protective properties of this agent have been poorly investigated, and deserve exploration in different neurotoxic models. In this study, we explored the effects of URB597 on oxidative damage to lipids and other major endpoints of toxicity in two neurotoxic models in vivo in rats (the first one produced by the mitochondrial neurotoxin 3-nitropropionic acid [3-NP], and the other generated by the striatal injection of the pro-oxidant toxin 6-hydroxidopamine [6-OHDA]) in order to provide further supporting evidence of its modulatory profile...
January 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28155214/ra-differentiation-enhances-dopaminergic-features-changes-redox-parameters-and-increases-dopamine-transporter-dependency-in-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-cells
#19
Fernanda M Lopes, Leonardo Lisbôa da Motta, Marco A De Bastiani, Bianca Pfaffenseller, Bianca W Aguiar, Luiz F de Souza, Geancarlo Zanatta, Daiani M Vargas, Patrícia Schönhofen, Giovana F Londero, Liana M de Medeiros, Valder N Freire, Alcir L Dafre, Mauro A A Castro, Richard B Parsons, Fabio Klamt
Research on Parkinson's disease (PD) and drug development is hampered by the lack of suitable human in vitro models that simply and accurately recreate the disease conditions. To counteract this, many attempts to differentiate cell lines, such as the human SH-SY5Y neuroblastoma, into dopaminergic neurons have been undertaken since they are easier to cultivate when compared with other cellular models. Here, we characterized neuronal features discriminating undifferentiated and retinoic acid (RA)-differentiated SH-SYSY cells and described significant differences between these cell models in 6-hydroxydopamine (6-OHDA) cytotoxicity...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28146406/humulus-japonicus-prevents-dopaminergic-neuron-death-in-6-hydroxydopamine-induced-models-of-parkinson-s-disease
#20
Young-Kyoung Ryu, Young Kang, Jun Go, Hye-Yeon Park, Jung-Ran Noh, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Sang-Seop Han, Won-Keun Oh, Chul-Ho Lee, Kyoung-Shim Kim
Humulus japonicus (HJ), popularly known as Japanese hops, is a traditional herbal medicine widely used for the treatment of pulmonary disease, skin disease, and hypertension in Korea. HJ exerts scavenging effects against reactive oxygen species (ROS), such as superoxide radical, hydroxyl radical, and hydrogen peroxide. Moreover, dysfunction and damage of mitochondria elicited by ROS are of critical importance in the pathogenesis of Parkinson's disease (PD). The present study aimed to examine neuroprotective potential of extracts of HJ using in vitro and in vivo 6-hydroxydopamine (6-OHDA) models...
February 2017: Journal of Medicinal Food
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