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Parkinson's disease animal models

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https://www.readbyqxmd.com/read/29028815/striatal-astrocytes-engulf-dopaminergic-debris-in-parkinson-s-disease-a-study-in-an-animal-model
#1
Ingrid Morales, Alberto Sanchez, Clara Rodriguez-Sabate, Manuel Rodriguez
The role of astrocytes in Parkinson's disease is still not well understood. This work studied the astrocytic response to the dopaminergic denervation. Rats were injected in the lateral ventricles with 6-hydroxydopamine (25μg), inducing a dopaminergic denervation of the striatum not accompanied by non-selective tissue damage. The dopaminergic debris were found within spheroids (free-spheroids) which retained some proteins of dopaminergic neurons (e.g., tyrosine hydroxylase, the dopamine transporter protein, and APP) but not others (e...
2017: PloS One
https://www.readbyqxmd.com/read/29027056/curcumin-affords-neuroprotection-and-inhibits-%C3%AE-synuclein-aggregation-in-lipopolysaccharide-induced-parkinson-s-disease-model
#2
Neha Sharma, Bimla Nehru
Parkinson's disease (PD) pathology is characterized by the abnormal accumulation and aggregation of the pre-synaptic protein α-synuclein in the dopaminergic neurons as Lewy bodies (LBs). Curcumin, which plays a neuroprotective role in various animal models of PD, was found to directly modulate the aggregation of α-synuclein in in vitro as well as in in vivo studies. While curcumin has been shown to exhibit strong anti-oxidant and anti-inflammatory properties, there are a number of other possible mechanisms by which curcumin may alter α-synuclein aggregation which still remains obscure...
October 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29024008/immunization-with-%C3%AE-synuclein-grp94-reshapes-peripheral-immunity-and-suppresses-microgliosis-in-a-chronic-parkinsonism-model
#3
Javier Villadiego, Adahir Labrador-Garrido, Jaime M Franco, Magdalena Leal-Lasarte, Erwin J De Genst, Christopher M Dobson, David Pozo, Juan J Toledo-Aral, Cintia Roodveldt
Neuroinflammation mediated by chronically activated microglia, largely caused by abnormal accumulation of misfolded α-synuclein (αSyn) protein, is known to contribute to the pathophysiology of Parkinson's disease (PD). In this work, based on the immunomodulatory activities displayed by particular heat-shock proteins (HSPs), we tested a novel vaccination strategy that used a combination of αSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used two different procedures, first, the adoptive transfer of splenocytes from αSyn/Grp94-immunized mice to recipient animals, and second, direct immunization with αSyn/Grp94, to study the effects in a chronic mouse MPTP-model of parkinsonism...
October 11, 2017: Glia
https://www.readbyqxmd.com/read/29021837/the-bssg-rat-model-of-parkinson-s-disease-progressing-towards-a-valid-predictive-model-of-disease
#4
REVIEW
Jackalina M Van Kampen, Harold A Robertson
ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder, classically considered a movement disorder. A great deal is known about the anatomical connections and neuropathology and pharmacological changes of PD, as they relate to the loss of dopaminergic function and the appearance of cardinal motor symptoms. Our understanding of the role of dopamine in PD has led to the development of effective pharmacological treatments of the motor symptoms in the form of dopamine replacement therapy using levodopa and dopaminergic agonists...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29021755/dj-1-inhibits-%C3%AE-synuclein-aggregation-by-regulating-chaperone-mediated-autophagy
#5
Chuan-Ying Xu, Wen-Yan Kang, Yi-Meng Chen, Tian-Fang Jiang, Jia Zhang, Li-Na Zhang, Jian-Qing Ding, Jun Liu, Sheng-Di Chen
α-Synuclein misfolding and aggregation play an important role in the pathogenesis of Parkinson's disease (PD). Loss of function and mutation of the PARK7/DJ-1 gene cause early-onset familial PD. DJ-1 can inhibit α-synuclein aggregation, and may function at an early step in the aggregation process. Soluble wild-type (WT) α-synuclein is mainly degraded by chaperone-mediated autophagy (CMA), and impairment of CMA is closely related to the pathogenesis of PD. Here, we investigated whether DJ-1 could reduce α-synuclein accumulation and aggregation by CMA...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29021298/prying-into-the-prion-hypothesis-for-parkinson-s-disease
#6
Patrik Brundin, Ronald Melki
In Parkinson's disease, intracellular α-synuclein inclusions form in neurons. We suggest that prion-like behavior of α-synuclein is a key component in Parkinson's disease pathogenesis. Although multiple molecular changes are involved in the triggering of the disease process, we propose that neuron-to-neuron transfer is a crucial event that is essential for Lewy pathology to spread from one brain region to another. In this review, we describe key findings in human postmortem brains, cultured cells, and animal models of disease that support the idea that α-synuclein can act as a prion...
October 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29019394/studies-on-16-17-pyrazoline-substituted-heterosteroids-as-anti-alzheimer-and-anti-parkinsonian-agents-using-lps-induced-neuroinflammation-models-of-mice-and-rats
#7
Ranjit Singh, Sridhar Thota, Ranju Bansal
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported as a neuroprotective steroid useful in the therapeutic management of neurodegenerative disorders such as AD and PD. Herein we report the synthesis and evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as neuroprotective agents using LPS-induced neuroinflammation animal models. Treatment with the pyrazoline substituted steroids considerably improved the LPS-induced learning, memory and movement deficits in animal models...
October 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29019159/alpha-lipoamide-ameliorates-motor-deficits-and-mitochondrial-dynamics-in-the-parkinson-s-disease-model-induced-by-6-hydroxydopamine
#8
Bo Zhou, Min Wen, Xin Lin, Yun-Hua Chen, Yun Gou, Yong Li, Yi Zhang, Hong-Wei Li, Lei Tang
The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are not yet fully elucidated; however, evidence from the in vitro and in vivo PD models suggest that mitochondrial dysfunction may play a major role in PD pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is a better cofactor for mitochondrial dehydrogenase with a stronger protective effect on mitochondria than lipoic acid. Identification of these protective effects of alpha lipoamide on mitochondria, together with the evidence that mitochondrial dysfunction plays a critical role in PD, we speculate that alpha lipoamide may exert a protective effect in PD by regulating the mitochondrial function...
October 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29017909/objectively-measuring-effects-of-electro-acupuncture-in-parkinsonian-rhesus-monkeys
#9
Rui Zhang, Anders H Andersen, Peter A Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M Gash, Richard Grondin, Zhiming Zhang
Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations...
October 7, 2017: Brain Research
https://www.readbyqxmd.com/read/29017893/chronic-inflammation-inflammaging-in-the-ageing-cochlea-a-novel-target-for-future-presbycusis-therapy
#10
Nathan Watson, Bo Ding, Xiaoxia Zhu, Robert D Frisina
Chronic, low-grade inflammation, or inflammaging, is a crucial contributor to various age-related pathologies and natural processes in aging tissue, including the nervous system. Over the past two decades, much effort has been done to understand the mechanisms of inflammaging in disease models such as type II diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease, and others. However, despite being the most prevalent neurodegenerative disorder, the number one communication disorder, and one of the top three chronic medical conditions of our aged population; little research has been conducted on the potential role of inflammation in age-related hearing loss (ARHL)...
October 7, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28994779/assessment-of-dopaminergic-homeostasis-in-mice-by-use-of-high-performance-liquid-chromatography-analysis-and-synaptosomal-dopamine-uptake
#11
Kathrine L Jensen, Annika H Runegaard, Pia Weikop, Ulrik Gether, Mattias Rickhag
Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) neurotransmission is strongly associated with several central nervous system-associated diseases such as Parkinson's disease, attention-deficit-hyperactivity disorder and drug addiction(1)(,)(2)(,)(3)(,)(4). Delineating disease mechanisms involving DA imbalance is critically dependent on animal models to mimic aspects of the diseases, and thus protocols that assess specific parts of the DA homeostasis are important to provide novel insights and possible therapeutic targets for these diseases...
September 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28990199/the-epigenetic-component-of-the-brain-response-to-electromagnetic-stimulation-in-parkinson-s-disease-patients-a-literature-overview
#12
REVIEW
Claudia Consales, Caterina Merla, Carmela Marino, Barbara Benassi
Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non-coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic-based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS)...
October 9, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/28988910/neuroprotection-and-neurorestoration-as-experimental-therapeutics-for-parkinson-s-disease
#13
REVIEW
Veronica Francardo, Yvonne Schmitz, David Sulzer, M Angela Cenci
Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD...
October 5, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28987031/using-minimalist-self-assembling-peptides-as-hierarchical-scaffolds-to-stabilize-growth-factors-and-promote-stem-cell-integration-in-the-injured-brain
#14
A L Rodriguez, K F Bruggeman, Y Wang, T Y Wang, R J Williams, C L Parish, D R Nisbet
Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease...
October 7, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28985333/nonhuman-primate-models-of-neurodegenerative-disorders
#15
Marina E Emborg
Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease are age-related neurodegenerative disorders characterized by progressive neuronal cell death. Although each disease has particular pathologies and symptoms, accumulated evidence points to similar mechanisms of neurodegeneration, including inflammation, oxidative stress, and protein aggregation. A significant body of research is ongoing to understand how these pathways affect each other and what ultimately triggers the onset of the disease. Experiments in nonhuman primates (NHPs) account for only 5% of all research in animals...
August 10, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28980404/preventive-and-therapeutic-potential-of-ascorbic-acid-in-neurodegenerative-diseases
#16
REVIEW
Morgana Moretti, Daiane Bittencourt Fraga, Ana Lúcia S Rodrigues
In this review, we summarize the involvement of ascorbic acid in neurodegenerative diseases by presenting available evidence on the behavioral and biochemical effects of this compound in animal models of neurodegeneration as well as the use of ascorbic acid as a therapeutic approach to alleviate neurodegenerative progression in clinical studies. Ascorbate, a reduced form of vitamin C, has gained interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration...
October 4, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28975502/l-serine-mediated-neuroprotection-includes-the-upregulation-of-the-er-stress-chaperone-protein-disulfide-isomerase-pdi
#17
R A Dunlop, J T Powell, J S Metcalf, G J Guillemin, P A Cox
The unfolded protein response (UPR) is a highly evolutionarily conserved response to endoplasmic reticulum (ER) stress, which functions to return cells to homeostasis or send them into apoptosis, depending on the degree of cellular damage. β-N-methylamino-L-alanine (L-BMAA) has been shown to induce ER stress in a variety of models and has been linked to several types of neurodegenerative disease including Guamanian amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC). L-Serine, an amino acid critical for cellular metabolism and neurological signaling, has been shown to be protective against L-BMAA-induced neurotoxicity in both animal and cell culture models...
October 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28973502/proteome-profile-of-different-rat-brain-regions-after-sarin-intoxication
#18
Kalyani Chaubey, Syed Imteyaz Alam, D P Nagar, Chandra Kant Waghmare, S C Pant, Lokendra Singh, Nalini Srivastava, Bijoy K Bhattacharya
Sarin is an organophosphorus chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is due to hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long term neuropathology referred as organophosphorus ester induced chronic neurotoxicity. However, the exact mechanism of chronic neuro-toxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long term CNS injury...
August 16, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28956336/regulation-of-striatal-neuron-activity-by-cyclic-nucleotide-signaling-and-phosphodiesterase-inhibition-implications-for-the-treatment-of-parkinson-s-disease
#19
Fernando E Padovan-Neto, Anthony R West
Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in the brain. Several classes of PDE enzymes with distinct tissue distributions, cyclic nucleotide selectivity, and regulatory factors are highly expressed in brain regions subserving cognitive and motor processes known to be disrupted in neurodegenerative diseases such as Parkinson's disease (PD). Furthermore, small-molecule inhibitors of several different PDE family members alter cyclic nucleotide levels and favorably enhance motor performance and cognition in animal disease models...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28953092/the-effects-of-mucuna-pruriens-extract-on-histopathological-and-biochemical-features-in-the-rat-model-of-ischemia
#20
Vanishri S Nayak, Nitesh Kumar, Antony S D'Souza, Sunil S Nayak, Sri P Cheruku, K Sreedhara Ranganath Pai
Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease...
September 25, 2017: Neuroreport
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