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Guo Ge, Cang Chen, Michael James Guderyon, Jingwei Liu, Zhixu He, Yanni Yu, Robert A Clark, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent neuroprotective properties in preclinical models of Parkinson's disease (PD), but challenges in GDNF delivery have been reported from clinical trials. To address this barrier, we developed a hematopoietic stem cell transplantation (HSCT) -based macrophage-mediated GDNF therapy platform. Here we introduced a regulatable lentiviral vector (LV-MSP-Tet-Off-hGDNF) in order to allow the expression of human GDNF to be adjusted or stopped by oral administration of doxycycline (Dox)...
March 21, 2018: Stem Cells and Development
Francisco Magalhães, Kaline Rocha, Victor Marinho, Jéssica Ribeiro, Thomaz Oliveira, Carla Ayres, Thalys Bento, Francisca Leite, Daya Gupta, Victor Hugo Bastos, Bruna Velasques, Pedro Ribeiro, Marco Orsini, Silmar Teixeira
BACKGROUND: Parkinson's disease is described as resulting from dopaminergic cells progressive degeneration, specifically in the substantia nigra pars compacta that influence the voluntary movements control, decision making and time perception. AIM: This review had a goal to update the relation between time perception and Parkinson's Disease. METHODOLOGY: We used the PRISMA methodology for this investigation built guided for subjects dopaminergic dysfunction in the time judgment, pharmacological models with levodopa and new studies on the time perception in Parkinson's Disease...
March 19, 2018: Journal of Biomedical Science
Sarah Schnitzler, Christian Johannes Hartmann, Stefan Jun Groiss, Lars Wojtecki, Alfons Schnitzler, Jan Vesper, Jan Hirschmann
OBJECTIVE: To assess whether high frequency oscillations (HFOs, >150 Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus. METHODS: We recorded intraoperative local field potentials from the ventral intermediate nucleus (VIM) of the thalamus in patients with Essential Tremor (N = 16), Parkinsonian Tremor (3), Holmes Tremor (2) and Dystonic Tremor (1) during implantation of electrodes for deep brain stimulation. Recordings were performed with up to five micro/macro-electrodes that were simultaneously advanced to the stereotactic target...
February 19, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Rosalia Crupi, Daniela Impellizzeri, Marika Cordaro, Rosalba Siracusa, Giovanna Casili, Maurizio Evangelista, Salvatore Cuzzocrea
Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD induced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model...
March 19, 2018: Molecular Neurobiology
Yong Wang, Ge-Juan Zhang, Yi-Na Sun, Lu Yao, Hui-Sheng Wang, Cheng-Xue Du, Li Zhang, Jian Liu
L-DOPA-induced dyskinesia (LID) is a frequent complication of chronic L-DOPA therapy in the clinical treatment of Parkinson's disease (PD). The pathogenesis of LID involves complex molecular mechanisms in the striatum. Metabolomics can shed light on striatal metabolic alterations in LID. In the present study, we compared metabolomics profiles of striatum tissue from Parkinsonian rats with or without dyskinetic symptoms after chronic L-DOPA administration. A liquid chromatography-mass spectrometry based global metabolomics method combined with multivariate statistical analyses were used to detect candidate metabolites associated with LID...
March 15, 2018: Behavioural Brain Research
Susanna Nuvoli, Barbara Palumbo, Simona Malaspina, Giuseppe Madeddu, Angela Spanu
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders...
March 20, 2018: Hellenic Journal of Nuclear Medicine
Sunao Mizumura, Kazuhiro Nishikawa, Akihiro Murata, Kosei Yoshimura, Nobutomo Ishii, Tadashi Kokubo, Miyako Morooka, Akiko Kajiyama, Atsuro Terahara
OBJECTIVE: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs...
March 15, 2018: Annals of Nuclear Medicine
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
Peter James Holland, Olivier Codol, Joseph M Galea
Despite increasing interest in the role of reward in motor learning, the underlying mechanisms remain ill-defined. In particular, the contribution of explicit processes to reward-based motor learning is unclear. To address this, we examined subject's (n=30) ability to learn to compensate for a gradually introduced 25⁰ visuomotor rotation with only reward-based feedback (binary success/failure). Only two-thirds of subjects (n=20) were successful at the maximum angle. The remaining subjects initially followed the rotation but after a variable number of trials began to reach at an insufficiently large angle and subsequently returned to near baseline performance (n=10)...
March 14, 2018: Journal of Neurophysiology
Jingjie Ge, Jianjun Wu, Shichun Peng, Ping Wu, Jian Wang, Huiwei Zhang, Yihui Guan, David Eidelberg, Chuantao Zuo, Yilong Ma
Progressive supranuclear palsy (PSP) is a rare movement disorder and often difficult to distinguish clinically from Parkinson's disease (PD) and multiple system atrophy (MSA) in early phases. In this study, we report reproducible disease-related topographies of brain network and regional glucose metabolism associated with PSP in clinically-confirmed independent cohorts of PSP, MSA, and PD patients and healthy controls in the USA and China. Using18 F-FDG PET images from PSP and healthy subjects, we applied spatial covariance analysis with bootstrapping to identify a PSP-related pattern (PSPRP) and estimate its reliability, and evaluated the ability of network scores for differential diagnosis...
March 13, 2018: Human Brain Mapping
Deborah Wearne, Amanda Genetti, Sam Restifo, Alina Harriss
OBJECTIVES: We aim to explore the importance of early diagnosis of dementia with Lewy bodies in order to facilitate effective psychiatric management. We present a case where delayed diagnosis stemming from an atypical presentation illustrates the complex issues involved in identifying and treating this type of dementia. CONCLUSIONS: We discuss the difficulty of diagnosis of this disorder in the absence of obvious memory dysfunction or parkinsonian symptoms. We use the case to draw attention to the limited availability of certain investigations and treatment options in Australia...
March 1, 2018: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
Kuo-Hsuan Chang, Guan-Chiun Lee, Chin-Chang Huang, Hung-Chou Kuo, Chiung-Mei Chen, Ya-Chin Hsiao, Hsuan-Chu Hsu, Ke-Jen Hsu, Chih-Hsin Lin, Chia Wen Chang, Guey-Jen Lee-Chen, Yih-Ru Wu
BACKGROUND: Mutations in the GRN (granulin precursor) are a frequent cause of frontotemporal dementia (FTD) and other atypical parkinsonian disorders. However, the frequency of GRN mutations in Asian patients with atypical parkinsonian disorders is still uncertain. METHODS: We screened GRN mutations by sequencing cDNA from 98 patients with FTD or atypical parkinsonian disorders. The functional properties of the identified mutation were evaluated by overexpression in human embryonic kidney (HEK)-293 cells...
February 28, 2018: Parkinsonism & related Disorders
Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Takahiro Maeki, Ryo Sasaki, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Chang Kweng Lim, Shigeru Tajima, Koji Abe
Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE...
March 9, 2018: Internal Medicine
Aline Souza Pagnussat, Ana F R Kleiner, Carlos R M Rieder, Anapaula Frantz, Jaira Ehlers, Camila Pinto, Gilson Dorneles, Carlos Alexandre Netto, Alessandra Peres, Manuela Galli
BACKGROUND: The decrease of Brain-Derived Neurotrophic Factor (BDNF) serum levels has been related to the pathophysiology of several neurodegenerative diseases as well as to neural plasticity and rehabilitation. Automated Mechanical Peripheral Stimulation (AMPS) has been investigated as a complementary therapy for Parkinson Disease (PD). OBJECTIVES: (1) to investigate the effects of AMPS on BDNF and Cortisol serum levels of subjects with PD; (2) to evidence the interplay between BDNF and Cortisol serum levels and the functional mobility improvement after AMPS treatment...
2018: Restorative Neurology and Neuroscience
Nicolas Veyres, Adjia Hamadjida, Philippe Huot
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson's disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism and psychosis. Three species have been used in the majority of studies, the macaque, marmoset and squirrel monkey, the latter much less so than the first 2 species. However, the predictive rate of each species at forecasting clinical efficacy, or lack thereof, is poorly documented...
March 9, 2018: Journal of Pharmacology and Experimental Therapeutics
Sujata Pradhan
Complexity of an animal's environment has been shown to affect structural and functional changes in the brain. Evidence from animal models of Parkinson's disease (PD) suggests that exercising in an enriched environment may protect against the onset of Parkinsonian symptoms in rats that are exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The variety of activities and visual interfaces that can be created using commercially available gaming devices provide cognitively stimulating as well as physically challenging environments for exercise...
March 9, 2018: Physiotherapy Theory and Practice
Agostinho Lemos, Rita Meloc, Antonio J Preto, Jose G Almeida, Irina S Moreira, M Natalia D S Cordeiro
Parkinson's Disease (PD) is a long-term neurodegenative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel anti-parkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding. For the last decades, L-3,4-DihydrOxyPhenylAlanine or levodopa (L-DOPA) has been the gold-standard therapy for the symptomatic treatment of motor dysfunctions associated to PD...
March 8, 2018: Current Neuropharmacology
Joshua I Hardt, Joel S Perlmutter, Christopher J Smith, Kevin L Quick, Ling Wei, Subhasish K Chakraborty, Laura L Dugan
BACKGROUND AND OBJECTIVES: Fullerene-based compounds are a novel class of molecules being developed for a variety of biomedical applications, with nearly 1000 publications in this area in the last 4 years alone. One such compound, the e,e,e-methanofullerene(60)-63-tris malonic acid (designated C3 ), is a potent catalytic superoxide dismutase mimetic which has shown neuroprotective efficacy in a number of animal models of neurologic disease, including Parkinsonian Macaca fascicularis monkeys...
March 8, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Leslie Citrome
Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD...
February 28, 2018: Journal of the Neurological Sciences
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