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https://www.readbyqxmd.com/read/27923670/early-and-progressive-microstructural-brain-changes-in-mice-overexpressing-human-%C3%AE-synuclein-detected-by-diffusion-kurtosis-imaging
#1
Amit Khairnar, Jana Ruda-Kucerova, Nikoletta Szabó, Eva Drazanova, Anas Arab, Birgit Hutter-Paier, Joerg Neddens, Peter Latta, Zenon Starcuk, Irena Rektorova
Diffusion kurtosis imaging (DKI) is sensitive in detecting α-Synuclein (α-Syn) accumulation-associated microstructural changes at late stages of the pathology in α-Syn overexpressing TNWT-61 mice. The aim of this study was to perform DKI in young TNWT-61 mice when α-Syn starts to accumulate and to compare the imaging results with an analysis of motor and memory impairment and α-Syn levels. Three-month-old (3mo) and six-month-old (6mo) mice underwent DKI scanning using the Bruker Avance 9.4 Tesla magnetic resonance imaging system...
December 3, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27919828/mucuna-pruriens-reduces-inducible-nitric-oxide-synthase-expression-in-parkinsonian-mice-model
#2
Satyndra Kumar Yadav, Sachchida Nand Rai, Surya Pratap Singh
Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp...
December 2, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#3
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27914043/a-revisit-to-quantitative-pet-with-18-f-fdopa-of-high-specific-activity-using-a-high-resolution-condition-in-view-of-application-to-regenerative-therapy
#4
Go Akamatsu, Akihito Ohnishi, Kazuki Aita, Hiroyuki Nishida, Yasuhiko Ikari, Masahiro Sasaki, Nobuo Kohara, Michio Senda
OBJECTIVE: With the advent of regenerative/cell therapy for Parkinson's disease (PD), (18)F-FDOPA has drawn new attention as a biomarker of the therapeutic that cannot be evaluated with radiopharmaceuticals for dopamine transporter. Since most previous (18)F-FDOPA PET studies were carried out many years ago with a PET scanner of lower resolution and with (18)F-FDOPA of low specific activity synthesized from (18)F-F2, we used a newer PET/CT scanner with a high-resolution condition and (18)F-FDOPA synthesized from (18)F-F(-) to re-evaluate this technique on normal subjects and patients with PD, together with D2 receptor imaging with (11)C-raclopride (RAC)...
December 2, 2016: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/27913104/d-ala2-gip-glu-pal-is-neuroprotective-in-a-chronic-parkinson-s-disease-mouse-model-and-increases-bndf-expression-while-reducing-neuroinflammation-and-lipid-peroxidation
#5
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Parkinson's disease (PD). Therefore, treatment to improve insulin resistance in T2DM may be useful for PD patients. Glucose dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family that can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. We had shown previously that D-Ala2-GIP-glu-PAL, a novel long-acting GIP analogue, can play a neuroprotective role in the PD mouse model induced by acute MPTP injection...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27911008/comparison-of-neuropathology-in-parkinson-s-disease-subjects-with-and-without-deep-brain-stimulation
#6
Gian D Pal, Bichun Ouyang, Geidy Serrano, Holly A Shill, Christopher Goetz, Glenn Stebbins, Leo Verhagen Metman, Erika Driver-Dunckley, Shyamal H Mehta, John N Caviness, Marwan N Sabbagh, Charles H Adler, Thomas G Beach
BACKGROUND: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. METHODS: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911006/lrrk2-levels-and-phosphorylation-in-parkinson-s-disease-brain-and-cases-with-restricted-lewy-bodies
#7
Nicolas Dzamko, Amanda M Gysbers, Rina Bandopadhyay, Marc F Bolliger, Akiko Uchino, Ye Zhao, Masaki Takao, Sandrine Wauters, Wilma D J van de Berg, Junko Takahashi-Fujigasaki, R Jeremy Nichols, Janice L Holton, Shigeo Murayama, Glenda M Halliday
BACKGROUND: Leucine rich repeat kinase 2 (LRRK2) is a promising target for the treatment of Parkinson's disease; however, little is known about the expression of LRRK2 in human brain and if/how LRRK2 protein levels are altered in Parkinson's disease. OBJECTIVES: We measured the protein levels of LRRK2 as well as its phosphorylation on serines 910, 935, and 973 in the postmortem brain tissue of Parkinson's disease patients and aged controls with and without Lewy bodies...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27906525/the-clinical-utility-of-qsm-disease-diagnosis-medical-management-and-surgical-planning
#8
REVIEW
Sarah Eskreis-Winkler, Yan Zhang, Jingwei Zhang, Zhe Liu, Alexey Dimov, Ajay Gupta, Yi Wang
Quantitative susceptibility mapping (QSM) is an MR technique that depicts and quantifies magnetic susceptibility sources. Mapping iron, the dominant susceptibility source in the brain, has many important clinical applications. Herein, we review QSM applications in the diagnosis, medical management, and surgical treatment of disease. To assist in early disease diagnosis, QSM can identify elevated iron levels in the motor cortex of amyotrophic lateral sclerosis patients, in the substantia nigra of Parkinson's disease (PD) patients, in the globus pallidus, putamen, and caudate of Huntington's disease patients, and in the basal ganglia of Wilson's disease patients...
December 1, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27904575/alpha-synuclein-structure-functions-and-interactions
#9
REVIEW
Fatemeh Nouri Emamzadeh
At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates. As a molecular biomarker for the detection of PD in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27904494/anti-apoptotic-effect-of-shudipingchan-granule-in-the-substantia-nigra-of-rat-models-of-parkinson-s-disease
#10
Qing Ye, Xiao-Lei Yuan, Jing He, Jie Zhou, Can-Xing Yuan, Xu-Ming Yang
Levodopa is the gold-standard treatment for Parkinson's disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson's disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903866/nigral-dopaminergic-pak4-prevents-neurodegeneration-in-rat-models-of-parkinson-s-disease
#11
So-Yoon Won, Mee-Hee Park, Soon-Tae You, Seung-Won Choi, Hyong-Kyu Kim, Catriona McLean, Suk-Chul Bae, Sang Ryong Kim, Byung Kwan Jin, Kun Ho Lee, Eun-Young Shin, Eung-Gook Kim
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons. We observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from PD patients and in rodent models of PD...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27902767/towards-a-non-human-primate-model-of-alpha-synucleinopathy-for-development-of-therapeutics-for-parkinson-s-disease-optimization-of-aav1-2-delivery-parameters-to-drive-sustained-expression-of-alpha-synuclein-and-dopaminergic-degeneration-in-macaque
#12
James B Koprich, Tom H Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M Brotchie
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27900485/serum-glutathione-peroxidase-xanthine-oxidase-and-superoxide-dismutase-activities-and-malondialdehyde-levels-in-patients-with-parkinson-s-disease
#13
Burcu Gökçe Çokal, Mustafa Yurtdaş, Selda Keskin Güler, Hafize Nalan Güneş, Ceyla Ataç Uçar, Bilal Aytaç, Zahide Esra Durak, Tahir Kurtuluş Yoldaş, İlker Durak, Hikmet Can Çubukçu
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Oxidative stress has been hypothesized to play a major role in the development of PD in various studies. This study assessed to investigate oxidative and anti-oxidative status in PD patients. We evaluated oxidant/antioxidant status by measuring serum malondialdehyde (MDA) levels, xanthine oxidase (XO) activities, and activities of antioxidant enzymes, namely, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)...
November 30, 2016: Neurological Sciences
https://www.readbyqxmd.com/read/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#14
Jeong Hwi Lee, Young Cheul Chung, Eugene Bok, Hankyu Lee, Sue Hee Huh, Ji Eun Lee, Byung Kwan Jin, Hyuk Wan Ko
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration...
November 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27899296/targeting-the-norepinephrinergic-system-in-parkinson-s-disease-and-related-disorders-the-locus-coeruleus-story
#15
Yannick Vermeiren, Peter P De Deyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are related, progressive and debilitating neurodegenerative disorders with hallmark features that include a variety of motor and non-motor symptoms (behavioral, autonomic and cognitive dysfunction). For almost half a century, the motor aspects have been attributed to Lewy pathology (LP) predominantly in the substantia nigra (SN), causing a major loss of dopaminergic neurons. However, the relative success of dopaminergic replacement therapies for alleviation of solely the parkinsonian features has prompted researchers to further explore other monoaminergic strategies which may tackle all PD-related aspects...
November 26, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27898200/transcranial-sonography-in-idiopathic-rem-sleep-behavior-disorder-and-multiple-system-atrophy
#16
Xudong Li, Shuang Xue, Shuhong Jia, Zhi Zhou, Yanan Qiao, Chunlei Hou, Kun Wei, Wenjing Zheng, Pei Rong, Jinsong Jiao
AIMS: We investigated preclinical abnormalities revealed by transcranial sonography (TCS) in patients with idiopathic REM sleep behavior disorder (iRBD) compared with those revealed in patients with multiple system atrophy (MSA) or Parkinson's disease (PD) and in normal controls. METHODS: Twenty-two patients with iRBD, 21 patients with MSA, 22 patients with PD and 21 normal controls were included in this study. All participants underwent one night of video-polysomnography (PSG) monitoring, and the sleep parameters were analyzed using Polysmith software and by visual analysis...
November 29, 2016: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/27895578/cognitive-performance-patterns-in-healthy-individuals-with-substantia-nigra-hyperechogenicity-and-early-parkinson-s-disease
#17
Rezzak Yilmaz, Susanne Gräber, Benjamin Roeben, Ulrike Suenkel, Anna-Katharina von Thaler, Sebastian Heinzel, Florian G Metzger, Gerhard W Eschweiler, Walter Maetzler, Daniela Berg, Inga Liepelt-Scarfone
Introduction: Hyperechogenicity of the substantia nigra (SN+) is a risk marker for Parkinson's disease (PD) which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD. Methods: Data of 262 healthy individuals with normal echogenicity (SN-) and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the "Consortium to Establish a Registry for Alzheimer's disease" test battery...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27893183/toxic-effects-of-human-and-rodent-variants-of-alpha-synuclein-in-vivo
#18
Natalie Landeck, Kerstin Buck, Deniz Kirik
In Parkinson's disease, abnormal alpha-synuclein (asyn) accumulation leads to the formation of soluble oligomeric species thought to be toxic to cells as well as intraneuronal inclusions. To date, the precise mechanisms leading to aggregation of asyn in the brain is not well understood. Previous studies in yeast, drosophila and transgenic mice suggested that a non-A beta component depleted version of human asyn [h-asyn(D70-83)] or human beta-synuclein (h-bsyn), naturally lacking this centrally located hydrophobic region, are less prone to form aggregates in vitro and are expected to be less toxic compared to h-asyn in vivo, although not all experimental studies unequivocally support the latter view...
November 28, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#19
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889621/identifying-non-toxic-doses-of-manganese-for-manganese-enhanced-magnetic-resonance-imaging-to-map-brain-areas-activated-by-operant-behavior-in-trained-rats
#20
Rita Gálosi, Csaba Szalay, Mihály Aradi, Gábor Perlaki, József Pál, Roy Steier, László Lénárd, Zoltán Karádi
Manganese-enhanced magnetic resonance imaging (MEMRI) offers unique advantages such as studying brain activation in freely moving rats, but its usefulness has not been previously evaluated during operant behavior training. Manganese in a form of MnCl2, at a dose of 20mg/kg, was intraperitoneally infused. The administration was repeated and separated by 24h to reach the dose of 40mg/kg or 60mg/kg, respectively. Hepatotoxicity of the MnCl2 was evaluated by determining serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin and protein levels...
November 24, 2016: Magnetic Resonance Imaging
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