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Parkinson's disease animal models

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https://www.readbyqxmd.com/read/29452179/massively-parallel-c-elegans-tracking-provides-multi-dimensional-fingerprints-for-phenotypic-discovery
#1
Michele Perni, Pavan K Challa, Julius B Kirkegaard, Ryan Limbocker, Mandy Koopman, Maarten C Hardenberg, Pietro Sormanni, Thomas Müller, Kadi L Saar, Lianne W Y Roode, Johnny Habchi, Giulia Vecchi, Nilumi W Fernando, Samuel Casford, Ellen A A Nollen, Michele Vendruscolo, Christopher M Dobson, Tuomas P J Knowles
BACKGROUND: The nematode worm C. elegans is a model organism widely used for studies of genetics and of human disease. The health and fitness of the worms can be quantified in different ways, such as by measuring their bending frequency, speed or lifespan. Manual assays, however, are time consuming and limited in their scope providing a strong motivation for automation. NEW METHOD: We describe the development and application of an advanced machine vision system for characterizing the behaviour of C...
February 13, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29448133/exposure-to-the-rock-inhibitor-fasudil-promotes-gliogenesis-of-neural-stem-cells-in-vitro
#2
Zubair Ahmed Nizamudeen, Lisa Chakrabarti, Virginie Sottile
Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17...
February 6, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29444523/a-novel-animal-model-of-parkinson-s-disease-using-optogenetics-representation-of-various-disease-stages-by-modulating-the-illumination-parameter
#3
Eun Jung Lee, Hyung Ho Yoon, Eun Suk Park, Joongkee Min, Sang Ryong Jeon
BACKGROUND: The classic animal model of Parkinson's disease (PD) using neurotoxin can only simulate fixed stages of the disease by causing irreversible damage to the nigrostriatal system. OBJECTIVES: To develop an optogenetic PD model that can modulate the severity of disease by optical stimulation by introducing the halorhodopsin (NpHR) gene into the substantia nigra compacta. METHODS: Fifteen rats received injections of engineered AAV with NpHR-YFP gene into the substantia nigra...
February 14, 2018: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/29433982/bimolecular-fluorescence-complementation-of-alpha-synuclein-demonstrates-its-oligomerization-with-dopaminergic-phenotype-in-mice
#4
Waijiao Cai, Danielle Feng, Michael A Schwarzschild, Pamela J McLean, Xiqun Chen
Alpha-synuclein (αSyn) is encoded by the first causal gene identified in Parkinson's disease (PD) and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animal models have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype αSyn by viral vectors in rodents recapitulates the loss of dopaminergic neurons from the substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC) of αSyn by recombinant adeno-associated virus facilitates detection of the toxic αSyn oligomers species...
January 31, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29432500/large-animals-as-potential-models-of-human-mental-and-behavioral-disorders
#5
REVIEW
Michał Danek, Janusz Danek, Aleksander Araszkiewicz
Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder)...
December 30, 2017: Psychiatria Polska
https://www.readbyqxmd.com/read/29428213/nigrostriatal-proteasome-inhibition-impairs-dopamine-neurotransmission-and-motor-function-in-minipigs
#6
Thea P Lillethorup, Andreas N Glud, Aage K O Alstrup, Trine W Mikkelsen, Erik H Nielsen, Hamed Zaer, Doris J Doudet, David J Brooks, Jens Christian H Sørensen, Dariusz Orlowski, Anne M Landau
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We translated this model to the Göttingen minipig by administering lactacystin into the medial forebrain bundle (MFB). Minipigs underwent positron emission tomography (PET) imaging with (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), a marker of vesicular monoamine transporter 2 availability, at baseline and three weeks after the unilateral administration of 100 μg lactacystin into the MFB...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29427747/nimodipine-attenuates-the-parkinsonian-neurotoxin-mptp-induced-changes-in-the-calcium-binding-proteins-calpain-and-calbindin
#7
Alpana Singh, Poonam Verma, Anu Raju, Kochupurackal P Mohanakumar
We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP+)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
February 7, 2018: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29427283/naringenin-decreases-%C3%AE-synuclein-expression-and-neuroinflammation-in-mptp-induced-parkinson-s-disease-model-in-mice
#8
Sugumar Mani, Sathiya Sekar, Rajamani Barathidasan, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Murugan Sevanan, Saravana Babu Chidambaram, Musthafa Mohamed Essa, Gilles J Guillemin, Meena Kishore Sakharkar
The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40-50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection...
February 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29422542/protection-of-nigral-dopaminergic-neurons-by-aav1-transduction-with-rheb-s16h-against-neurotoxic-inflammation-in-vivo
#9
Sehwan Kim, Gyeong Joon Moon, Yong-Seok Oh, Jungha Park, Won-Ho Shin, Jae Yeong Jeong, Kwang Shik Choi, Byung Kwan Jin, Nikolai Kholodilov, Robert E Burke, Hyung-Jun Kim, Chang Man Ha, Seok-Geun Lee, Sang Ryong Kim
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2)...
February 9, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29421187/activation-of-the-subthalamic-nucleus-suppressed-by-high-frequency-stimulation-a-c-fos-immunohistochemical-study
#10
Safa Shehab, Crystal D'souza, Milos Ljubisavljevic, Peter Redgrave
Deep Brain Stimulation applied at high frequency (HFS) to the subthalamic nucleus (STN) is used to ameliorate the symptoms of Parkinson's disease. The mechanism by which this is achieved remains controversial. In particular, it is uncertain whether HFS has a suppressive or excitatory action locally within the STN. Brief exposure of rats to ether anaesthesia evokes pathological burst firing and associated expression of the immediate early gene c-Fos in STN neurons. We used this ether model of STN activation to test the effect of a range of HFS parameters on c-Fos expression evoked by the anesthetic...
February 5, 2018: Brain Research
https://www.readbyqxmd.com/read/29419747/voluntary-physical-exercise-improves-subsequent-motor-and-cognitive-impairments-in-a-rat-model-of-parkinson-s-disease
#11
Shih-Chang Hsueh, Kai-Yun Chen, Jing-Huei Lai, Chung-Che Wu, Yu-Wen Yu, Yu Luo, Tsung-Hsun Hsieh, Yung-Hsiao Chiang
BACKGROUND: Parkinson's disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. METHODS: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD...
February 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29418019/new-developments-in-genetic-rat-models-of-parkinson-s-disease
#12
REVIEW
Rose B Creed, Matthew S Goldberg
Preclinical research on Parkinson's disease has relied heavily on mouse and rat animal models. Initially, PD animal models were generated primarily by chemical neurotoxins that induce acute loss of dopaminergic neurons in the substantia nigra. On the discovery of genetic mutations causally linked to PD, mice were used more than rats to generate laboratory animals bearing PD-linked mutations because mutagenesis was more difficult in rats. Recent advances in technology for mammalian genome engineering and optimization of viral expression vectors have increased the use of genetic rat models of PD...
February 8, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29417473/impact-of-coffee-and-cacao-purine-metabolites-on-neuroplasticity-and-neurodegenerative-disease
#13
Simonetta Camandola, Natalie Plick, Mark P Mattson
Increasing evidence suggests that regular consumption of coffee, tea and dark chocolate (cacao) can promote brain health and may reduce the risk of age-related neurodegenerative disorders. However, the complex array of phytochemicals in coffee and cacao beans and tea leaves has hindered a clear understanding of the component(s) that affect neuronal plasticity and resilience. One class of phytochemicals present in relatively high amounts in coffee, tea and cacao are methylxanthines. Among such methylxanthines, caffeine has been the most widely studied and has clear effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer's disease and Parkinson's disease...
February 8, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29416594/pink1-suppresses-alpha-synuclein-induced-neuronal-injury-a-novel-mechanism-in-protein-phosphatase-2a-activation
#14
Weiwei Yang, Xue Wang, Jia Liu, Chunli Duan, Ge Gao, Lingling Lu, Shun Yu, Hui Yang
Alpha-synuclein (α-Syn) and phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase (PINK) 1 are proteins found in Lewy bodies, which are a pathological hallmark of Parkinson's disease (PD). PINK1 overexpression suppresses α-Syn-induced phenotypes and increases lifespan and health in an animal model of PD. It has been suggested that the two proteins regulate protein phosphatase (PP) 2A activity, but the underlying mechanisms and neuroprotective action of PP2A against PD-associated pathology are unknown...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411055/improved-neuroprotective-effect-of-resveratrol-nanoparticles-as-evinced-by-abrogation-of-rotenone-induced-behavioral-deficits-and-oxidative-and-mitochondrial-dysfunctions-in-rat-model-of-parkinson-s-disease
#15
Suresh Palle, Prasad Neerati
The objective of the present study was to evaluate the protective effect of resveratrol nanoparticles (NRSV) against rotenone-induced neurodegeneration in rats. NRSV were prepared by temperature-controlled antisolvent precipitation method and characterized for its particle size, shape, and dissolution properties. Moreover, NRSV effects compared with the free resveratrol (RSV). Animals were divided into four groups: (I) control, (II) rotenone (2 mg/kg s.c.), (III) RSV (40 mg/kg, p.o.) + rotenone, and (IV) NRSV (40 mg/kg, p...
February 6, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29409959/ahr-and-cyp1a2-genotypes-both-affect-susceptibility-to-motor-deficits-following-gestational-and-lactational-exposure-to-polychlorinated-biphenyls
#16
Breann T Colter, Helen Frances Garber, Sheila M Fleming, Jocelyn Phillips Fowler, Gregory D Harding, Molly Kromme Hooven, Amy Ashworth Howes, Smitha Krishnan Infante, Anna L Lang, Melinda Curran MacDougall, Melinda Stegman, Kelsey Rae Taylor, Christine Perdan Curran
Polychlorinated biphenyls (PCBs) are persistent organic pollutants known to cause adverse health effects and linked to neurological deficits in both human and animal studies. Children born to exposed mothers are at highest risk of learning and memory and motor deficits. We developed a mouse model that mimics human variation in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) to determine if genetic variation increases susceptibility to developmental PCB exposure. In our previous studies, we found that high-affinity AhrbCyp1a2(-/-) and poor-affinity AhrdCyp1a2(-/-) knockout mice were most susceptible to learning and memory deficits following developmental PCB exposure compared with AhrbCyp1a2(+/+) wild type mice (C57BL/6J strain)...
January 30, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29408408/combination-of-cdnf-and-deep-brain-stimulation-decreases-neurological-deficits-in-late-stage-model-parkinson-s-disease
#17
Antti Huotarinen, Anna-Maija Penttinen, Susanne Bäck, Merja H Voutilainen, Ulrika Julku, T Petteri Piepponen, Pekka T Männistö, Mart Saarma, Raimo Tuominen, Aki Laakso, Mikko Airavaara
Several neurotrophic factors (NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease (PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation (STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched...
February 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29403026/impaired-wnt-signaling-in-dopamine-containing-neurons-is-associated-with-pathogenesis-in-a-rotenone-triggered-drosophila-parkinson-s-disease-model
#18
Flora Stephano, Stella Nolte, Julia Hoffmann, Samar El-Kholy, Jakob von Frieling, Iris Bruchhaus, Christine Fink, Thomas Roeder
Parkinson's disease, which is the one of the most common neurodegenerative movement disorder, is characterized by a progressive loss of dopamine containing neurons. The mechanisms underlying disease initiation and development are not well understood and causative therapies are currently not available. To elucidate the molecular processes during early stages of Parkinson's disease, we utilized a Drosophila model. To induce Parkinson's disease-like phenotypes, we treated flies with the pesticide rotenone and isolated dopamine producing neurons of animals that were at an early disease stage...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29402504/novel-dual-glp-1-gip-receptor-agonists-show-neuroprotective-effects-in-alzheimer-s-and-parkinson-s-disease-models
#19
REVIEW
Christian Hölscher
Type 2 diabetes is a risk factor for several chronic neurodegenerative disorders such as Alzheimer's or Parkinson's disease. The link appears to be insulin de-sensitisation in the brain. Insulin is an important neuroprotective growth factor. GLP-1 and GIP are growth factors that re-sensitise insulin and GLP-1 mimetics are used in the clinic to treat diabetes. GLP-1 and GIP mimetics initially designed to treat diabetes show good protective effects in animal models of Alzheimer's and Parkinson's disease. Based on these results, several clinical trials have shown first encouraging effects in patients with Alzheimer's or Parkinson' disease...
January 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29400668/best-practices-for-generating-and-using-alpha-synuclein-pre-formed-fibrils-to-model-parkinson-s-disease-in-rodents
#20
Nicole K Polinski, Laura A Volpicelli-Daley, Caryl E Sortwell, Kelvin C Luk, Nunilo Cremades, Lindsey M Gottler, Jessica Froula, Megan F Duffy, Virginia M Lee, Terina N Martinez, Kuldip D Dave
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique new model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form-the aSyn pre-formed fibril (aSyn PFF)-which is then injected into the brain or introduced to the media in culture...
January 30, 2018: Journal of Parkinson's Disease
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