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https://www.readbyqxmd.com/read/28733899/6-ohda-induces-oxidation-of-f-box-protein-fbw7%C3%AE-by-chaperone-mediated-autophagy-in-parkinson-s-model
#1
Xiufeng Wang, Heng Zhai, Fang Wang
Parkinson's disease (PD) is the most common movement disorder disease, and its pathological feature is the degenerative loss of dopaminergic neurons in the substantia nigra compacta (SNc). In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanisms. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals' models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity...
July 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28728428/consequence-of-dopamine-d2-receptor-blockade-on-the-hyperphagic-effect-induced-by-cannabinoid-cb1-and-cb2-receptors-in-layers
#2
M Khodadadi, M Zendehdel, A Baghbanzadeh, V Babapour
1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor induced hyperphagia in 3-h feed-deprived (FD3) neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB1 receptor agonist; 2 µg) and co-adminstration of L-DOPA (125 nmol) plus 2-AG (2 µg)...
July 21, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28726961/functional-single-walled-carbon-nanotubes-car-for-targeting-dopamine-delivery-into-the-brain-of-parkinsonian-mice
#3
Qing Guo, Huihui You, Xu Yang, Bencheng Lin, Zhihong Zhu, Zhisong Lu, Xiaoxiao Li, Yun Zhao, Lin Mao, Shiping Shen, Haoyan Cheng, Jiting Zhang, Lingfu Deng, Jianhua Fan, Zhuge Xi, Rui Li, Chang Ming Li
Current treatments for Parkinson's disease (PD) are limited, partly due to the difficulties posed by the blood brain barrier (BBB) when delivering drugs to the brain. Herein, we explore the feasibility and efficacy of functional single-walled carbon nanotubes 'CAR' (SWCNT-PEGs-Lf) which carry and target-deliver dopamine (DA) to the brain in PD mice for treatment. SWCNTs can penetrate the cell-membrane remarkably, with the characteristics including high drug-loading and pH-dependent therapeutic unloading capacities...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28713483/the-treadmill-exercise-protects-against-dopaminergic-neuron-loss-and-brain-oxidative-stress-in-parkinsonian-rats
#4
Roberta Oliveira da Costa, Carlos Vinicius Jataí Gadelha-Filho, Ayane Edwiges Moura da Costa, Mariana Lima Feitosa, Dayane Pessoa de Araújo, Jalles Dantas de Lucena, Pedro Everson Alexandre de Aquino, Francisco Arnaldo Viana Lima, Kelly Rose Tavares Neves, Glauce Socorro de Barros Viana
Parkinson's disease (PD), a progressive neurological pathology, presents motor and nonmotor impairments. The objectives were to support data on exercise benefits to PD. Male Wistar rats were distributed into sham-operated (SO) and 6-OHDA-lesioned, both groups without and with exercise. The animals were subjected to treadmill exercises (14 days), 24 h after the stereotaxic surgery and striatal 6-OHDA injection. Those from no-exercise groups stayed on the treadmill for the same period and, afterwards, were subjected to behavioral tests and euthanized for neurochemical and immunohistochemical assays...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28710704/systemic-analysis-of-mirnas-in-pd-stress-condition-mir-5701-modulates-mitochondrial-lysosomal-cross-talk-to-regulate-neuronal-death
#5
Paresh Prajapati, Lakshmi Sripada, Kritarth Singh, Milton Roy, Khyati Bhatelia, Pooja Dalwadi, Rajesh Singh
Parkinson's disease (PD) is complex neurological disorder and is prevalent in the elderly population. This is primarily due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) region of the brain. The modulators of the selective loss of dopaminergic neurons in PD are still not well understood. The small non-coding RNAs specifically miRNAs fine-tune the protein levels by post-transcriptional gene regulation. The role of miRNAs in PD pathogenesis is still not well characterized. In the current study, we identified the miRNA expression pattern in 6-OHDA-induced PD stress condition in SH-SY5Y, dopaminergic neuronal cell line...
July 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28707266/6-ohda-lesioned-adult-zebrafish-as-a-useful-parkinson-s-disease-model-for-dopaminergic-neuroregeneration
#6
Yuganthini Vijayanathan, Fei Tieng Lim, Siong Meng Lim, Chiau Ming Long, Maw Pin Tan, Abu Bakar Abdul Majeed, Kalavathy Ramasamy
Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6...
July 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28702721/peptides-semax-and-selank-affect-the-behavior-of-rats-with-6-ohda-induced-pd-like-parkinsonism
#7
P A Slominsky, M I Shadrina, T A Kolomin, A V Stavrovskaya, E V Filatova, L A Andreeva, S N Illarioshkin, N F Myasoedov
Parkinson's disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals...
May 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28701075/the-effect-of-orexin-a-on-motor-and-cognitive-functions-in-a-rat-model-of-parkinson-s-disease
#8
Zahra Hadadianpour, Farangis Fatehi, Fateme Ayoobi, Ayat Kaeidi, Ali Shamsizadeh, Iman Fatemi
OBJECTIVE:  The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson's disease. METHODS: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests...
July 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28697377/absence-of-regulator-of-g-protein-signaling-4-does-not-protect-against-dopamine-neuron-dysfunction-and-injury-in-the-mouse-6-hydroxydopamine-lesion-model-of-parkinson-s-disease
#9
Amer Ashrafi, Pierre Garcia, Heike Kollmus, Klaus Schughart, Antonio Del Sol, Manuel Buttini, Enrico Glaab
Regulator of G-protein signaling 4 (RGS4), a member of the RGS family of proteins that inactivate G-proteins, has gained interest as a potential drug target for neurological disorders, such as epilepsy and Parkinson's disease (PD). In the case of PD, the main current options for alleviating motor symptoms are dopamine replacement therapies, which have limitations because of side effects and reduced effectiveness over the long term. Research on new nondopaminergic PD drug targets has indicated that inhibition of RGS4 could be an effective adjuvant treatment option...
June 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28695985/intrastriatal-administration-of-botulinum-neurotoxin-a-normalizes-striatal-d2-r-binding-and-reduces-striatal-d1-r-binding-in-male-hemiparkinsonian-rats
#10
Franziska Wedekind, Angela Oskamp, Markus Lang, Alexander Hawlitschka, Karl Zilles, Andreas Wree, Andreas Bauer
Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7)...
July 11, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28694175/daily-consumption-of-methylene-blue-reduces-attentional-deficits-and-dopamine-reduction-in-a-6-ohda-model-of-parkinson-s-disease
#11
Elizabeth S Smith, Madeline E Clark, Gwendolyn A Hardy, David J Kraan, Elisa Biondo, F Gonzalez-Lima, Lawrence K Cormack, Marie Monfils, Hongjoo J Lee
Recently, alternative drug therapies for Parkinson's disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might be the use of methylene blue (MB), an antioxidant and metabolic enhancer. MB has been shown to improve cognitive function in both intact rodents and rodent disease models...
July 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28688199/differential-expression-of-park2-splice-isoforms-in-an-in-vitro-model-of-dopaminergic-like-neurons-exposed-to-toxic-insults-mimicking-parkinson-s-disease
#12
Valentina La Cognata, Grazia Maugeri, Agata Grazia D'Amico, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Mutations in PARK2 (or parkin) are responsible for 50% of cases of autosomal-recessive juvenile-onset Parkinson's disease (PD). To date, 21 alternative splice variants of the human gene have been cloned. Yet most studies have focused on the full-length protein, whereas the spectrum of the parkin isoforms expressed in PD has never been investigated. In this study, the role of parkin proteins in PD neurodegeneration was explored for the first time by analyzing their expression profile in an in vitro model of PD...
July 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28687605/alterations-in-functional-cortical-hierarchy-in-hemiparkinsonian-rats
#13
B N Jávor-Duray, M Vinck, M van der Roest, E Bezard, H W Berendse, T Boraud, P Voorn
Parkinson's disease and experimentally induced hemiparkinsonism are characterized by increased beta-synchronization between cortical and subcortical areas. This change in beta-connectivity might reflect either a symmetric increase in interareal influences or asymmetric changes in directed influences among brain areas. We assessed patterns of functional and directed connectivity within and between striatum and six cortical sites in each hemisphere of the hemiparkinsonian rat model. Local field potentials were recorded in resting and walking states, before and after unilateral 6-hydroxydopamine lesion...
July 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28687484/participation-of-locus-coeruleus-in-breathing-control-in-female-rats
#14
Débora de Carvalho, Luis Gustavo A Patrone, Danuzia A Marques, Mariane C Vicente, Raphael E Szawka, Janete A Anselmo-Franci, Kênia C Bícego, Luciane H Gargaglioni
Several evidences indicate that the locus coeruleus (LC) is involved in central chemoreception responding to CO2/pH and displaying a high percentage of chemosensitive neurons (>80%). However, there are no studies about the LC-mediated hypercapnic ventilation performed in females. Therefore, we assessed the role of noradrenergic LC neurons in non-ovariectomized (NOVX), ovariectomized (OVX) and estradiol (E2)-treated ovariectomized (OVX+E2) rats in respiratory response to hypercapnia, using a 6-hydroxydopamine (6-OHDA) - lesion model...
July 4, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28681934/3-4-dihydroxybenzalacetone-and-caffeic-acid-phenethyl-ester-induce-preconditioning-er-stress-and-autophagy-in-sh-sy5y-cells
#15
Ryoichi Tomiyama, Ken Takakura, Shouhei Takatou, Thuong Manh Le, Takumi Nishiuchi, Yutaka Nakamura, Tetsuya Konishi, Seiichi Matsugo, Osamu Hori
3,4-dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH-SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress-related genes such as HSPA5, HYOU1, DDIT3, and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1, GCLM, and NQO1 increased to a larger extent in response to DBL treatment...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28680396/botulinum-neurotoxin-a-injected-ipsilaterally-or-contralaterally-into-the-striatum-in-the-rat-6-ohda-model-of-unilateral-parkinson-s-disease-differently-affects-behavior
#16
Veronica A Antipova, Carsten Holzmann, Oliver Schmitt, Andreas Wree, Alexander Hawlitschka
Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28672859/astrocytic-expression-of-gsta4-is-associated-to-dopaminergic-neuroprotection-in-a-rat-6-ohda-model-of-parkinson-s-disease
#17
Michael Jewett, Itzia Jimenez-Ferrer, Maria Swanberg
Idiopathic Parkinson's disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD...
June 26, 2017: Brain Sciences
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
#18
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/28634107/chronic-pramipexole-treatment-induces-compulsive-behavior-in-rats-with-6-ohda-lesions-of-the-substantia-nigra-and-ventral-tegmental-area
#19
D Dardou, L Reyrolle, C Chassain, F Durif
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions...
June 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28627694/investigation-of-the-neuroprotective-effects-of-a-novel-synthetic-compound-via-the-mitochondrial-pathway
#20
Di Wang, Shuang Hu, Junrong Zhang, Qiuyue Li, Xinyu Liu, Yu Li
The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6‑hydroxydopamine (6‑OHDA) and L‑glutamic acid (L‑Glu) neurotoxin‑induced cell injury and the potential mechanisms involved. 5zou is a 2, 2‑disubstituted 1,2‑dihydropyridine. PC12 cells were treated with 6‑OHDA and L‑Glu to establish neurotoxic cell models. MTT assay, DCFH‑DA staining, Fluo‑4‑AM staining, JC‑1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B‑cell lymphoma‑2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL)...
August 2017: Molecular Medicine Reports
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