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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#1
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212694/suvorexant-induced-dream-enactment-behavior-in-parkinson-disease-a-case-report
#2
Hiromitsu Tabata, Akira Kuriyama, Fusae Yamao, Hiroshi Kitaguchi, Katsuro Shindo
Suvorexant is a new insomnia drug, and it is generally safe and well tolerated. Here, we report a rare but potentially important adverse effect of suvorexant in a patient with Parkinson disease.
February 15, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28208916/delirium-in-parkinson-s-disease-a-cocktail-diagnosis
#3
Robin George Manappallil
Mental disturbances have been described in patients with Parkinson's Disease (PD). Of these, the common conditions are delirium and psychosis. Delirium has been attributed to change of environment, especially hospital stay and infections; while psychosis is due to drugs like dopamine agonists. This is a case of a 75-year-old male, on levodopa therapy for PD, who presented with delirium and ended up with a cocktail diagnosis: Cryptococcal meningitis, Hashimoto's Encephalopathy (HE), Urinary tract infection with acute renal failure, Uremic encephalopathy and Levodopa induced psychosis...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#4
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#5
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28192111/effects-of-progesterone-administered-after-mptp-on-dopaminergic-neurons-of-male-mice
#6
Nadhir Litim, Marc Morissette, Thérèse Di Paolo
Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28178069/montelukast-treatment-protects-nigral-dopaminergic-neurons-against-microglial-activation-in-the-6-hydroxydopamine-mouse-model-of-parkinson-s-disease
#7
Hannah Jang, Sehwan Kim, Jae Man Lee, Yong-Seok Oh, Sang Myun Park, Sang Ryong Kim
Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions...
February 7, 2017: Neuroreport
https://www.readbyqxmd.com/read/28155214/ra-differentiation-enhances-dopaminergic-features-changes-redox-parameters-and-increases-dopamine-transporter-dependency-in-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-cells
#8
Fernanda M Lopes, Leonardo Lisbôa da Motta, Marco A De Bastiani, Bianca Pfaffenseller, Bianca W Aguiar, Luiz F de Souza, Geancarlo Zanatta, Daiani M Vargas, Patrícia Schönhofen, Giovana F Londero, Liana M de Medeiros, Valder N Freire, Alcir L Dafre, Mauro A A Castro, Richard B Parsons, Fabio Klamt
Research on Parkinson's disease (PD) and drug development is hampered by the lack of suitable human in vitro models that simply and accurately recreate the disease conditions. To counteract this, many attempts to differentiate cell lines, such as the human SH-SY5Y neuroblastoma, into dopaminergic neurons have been undertaken since they are easier to cultivate when compared with other cellular models. Here, we characterized neuronal features discriminating undifferentiated and retinoic acid (RA)-differentiated SH-SYSY cells and described significant differences between these cell models in 6-hydroxydopamine (6-OHDA) cytotoxicity...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28148299/propagation-of-pathological-%C3%AE-synuclein-in-marmoset-brain
#9
Aki Shimozawa, Maiko Ono, Daisuke Takahara, Airi Tarutani, Sei Imura, Masami Masuda-Suzukake, Makoto Higuchi, Kazuhiko Yanai, Shin-Ichi Hisanaga, Masato Hasegawa
α-Synuclein is a defining, key component of Lewy bodies and Lewy neurites in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), as well as glial cytoplasmic inclusions in multiple system atrophy (MSA). The distribution and spreading of these pathologies are closely correlated with disease progression. Recent studies have revealed that intracerebral injection of synthetic α-synuclein fibrils or pathological α-synuclein prepared from DLB or MSA brains into wild-type or transgenic animal brains induced prion-like propagation of phosphorylated α-synuclein pathology...
February 2, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28148284/rasagiline-induced-severe-recurrent-hypoglycemia-in-a-young-woman-without-diabetes-a-case-report
#10
Fawzi A Bachet Ibrahim, Fauzia Rashid, Azza A Bin Hussain, Fatheya Alawadi, A Bashier
BACKGROUND: We report a case of a patient with recurrent severe hypoglycemia after initiating the drug rasagiline (Azilect) for Parkinson disease. CASE PRESENTATION: A 25-year-old Emirati woman who had been diagnosed with Parkinson disease due to a genetic mutation since the age of 18 years presented to our hospital. She had been treated with a rotigotine patch 2 mg per day along with carbidopa + levodopa + entacapone 25 mg/100 mg/200 mg (Stalevo) over these years...
February 2, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28145852/safranal-prevents-rotenone-induced-oxidative-stress-and-apoptosis-in-an-in-vitro-model-of-parkinson-s-disease-through-regulating-keap1-nrf2-signaling-pathway
#11
P-K Pan, L-Y Qiao, X-N Wen
Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenone-induced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28130646/the-effect-of-mirtazapine-on-dopaminergic-psychosis-and-dyskinesia-in-the-parkinsonian-marmoset
#12
Adjia Hamadjida, Stephen G Nuara, Nicolas Veyres, Imane Frouni, Cynthia Kwan, Lamia Sid-Otmane, Mery-Jane Harraka, Jim C Gourdon, Philippe Huot
BACKGROUND: Parkinson's disease (PD) psychosis is encountered in as many as 50% of patients with advanced disease. Treatment options for PD psychosis are few. In fact, only clozapine and pimavanserin have shown efficacy in randomised controlled trials. Clinicians are often reluctant to prescribe the former, due to the risk of agranulocytosis, while the latter is not widely available yet. Because it is already clinically available and exhibits high affinity for serotonin 2A receptors, a target with which both clozapine and pimavanserin interact, we hypothesised that the anti-depressant mirtazapine might be effective to alleviate PD psychosis...
January 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28126506/-other-causes-of-parkinsonism
#13
Christine Tranchant
Numerous causes may induce parkinsonism, and in case of Parkinsonism, l-dopa resistance, associated neurological signs, early falls, early dysautonomia or early cognitive disorders are the main red flags which should lead to exclude Parkinson's disease. Drug-induced parkinsonism and in young people, Wilson disease, should always be searched. Lower limbs parkinsonism is often due to vascular lesions. Multiple systemic atrophy, supranuclear palsy, Lewy body disease and the rarer corticobasal degeneration, each have specific clinical signs...
January 23, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28123025/sodium-pumps-mediate-activity-dependent-changes-in-mammalian-motor-networks
#14
Laurence D Picton, Filipe Nascimento, Matthew J Broadhead, Keith T Sillar, Gareth B Miles
: Ubiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects that were dependent on the presence of the neuromodulator dopamine...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28122575/drug-induced-parkinson-s-disease-modulates-protein-kinase-a-and-olfactory-marker-protein-in-the-mouse-olfactory-bulb
#15
Carla Mucignat, Antonio Caretta
BACKGROUND: Olfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice. FINDINGS: Lesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission...
January 26, 2017: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/28122428/clinical-features-indicating-nigrostriatal-dopaminergic-degeneration-in-drug-induced-parkinsonism
#16
Seung Ha Lee, Han Kyeol Kim, Young Gun Lee, Chul Hyoung Lyoo, Sung Jun Ahn, Myung Sik Lee
OBJECTIVE: Patients with drug-induced parkinsonism (DIP) may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. METHODS: Forty-one DIP patients were classified into normal and abnormal [(18)F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. RESULTS: Twenty-eight patients had normal (Group I) and 13 patients had abnormal (Group II) scans...
January 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28112685/chemogenetic-stimulation-of-striatal-projection-neurons-modulates-responses-to-parkinson-s-disease-therapy
#17
Cristina Alcacer, Laura Andreoli, Irene Sebastianutto, Johan Jakobsson, Tim Fieblinger, Maria Angela Cenci
Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways' contribution to different motor features using SPN type-specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA-induced dyskinesia (LID mice)...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28109635/impact-of-high-cholesterol-in-a-parkinson-s-disease-model-prevention-of-lysosomal-leakage-versus-stimulation-of-%C3%AE-synuclein-aggregation
#18
Ida Eriksson, Sangeeta Nath, Per Bornefall, Ana Maria Villamil Giraldo, Karin Öllinger
Parkinson's disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated α-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), we found that MPP(+)-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells...
January 16, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#19
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder, and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron(II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron(II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28100851/effects-of-propofol-on-oxidative-stress-parameters-in-selected-parts-of-the-brain-in-a-rat-model-of-parkinson-disease
#20
Ewa Romuk, Wioletta Szczurek, Przemysław Nowak, Marta Skowron, Bernard Prudel, Edyta Hudziec, Ewa Chwalińska, Ewa Birkner
INTRODUCTION: Propofol is an intravenous sedative-hypnotic agent that is commonly used to induce and maintain general anaesthesia. This drug has antioxidant properties, which are partly caused by a phenolic structure similar to α-tocopherol. The present study aimed to evaluate the effect of propofol on the level of oxidative stress biomarkers in the frontal cortex, striatum, thalamus, hippocampus and cerebellum in rats with experimental Parkinson's disease (PD). MATERIAL/METHODS: The experiment was performed on 24 male Wistar rats assigned to the following groups: 1 - control; 2 - PD; 3 - PD with propofol...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
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