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Analía G Karadayian, Gabriela Malanga, Analía Czerniczyniec, Paulina Lombardi, Juanita Bustamante, Silvia Lores-Arnaiz
Alcohol hangover (AH) is the pathophysiological state after a binge-like drinking. We have previously demonstrated that AH induced bioenergetics impairments in a total fresh mitochondrial fraction in brain cortex and cerebellum. The aim of this work was to determine free radical production and antioxidant systems in non-synaptic mitochondria and synaptosomes in control and hangover animals. Superoxide production was not modified in non-synaptic mitochondria while a 17.5% increase was observed in synaptosomes...
April 24, 2017: Free Radical Biology & Medicine
Laetitia Lemoine, Laure Saint-Aubert, Inger Nennesmo, Per-Göran Gillberg, Agneta Nordberg
Hyperphosphorylated tau protein deposits and, inflammatory processes are characteristic components of Alzheimer disease (AD) pathology. We here aimed to visualize in vitro the distribution of tau deposits and activated astrocytes across the cortical layers in autopsy AD brain tissue using the radiotracers (3)H-THK5117 and (3)H-deprenyl. (3)H-THK5117 and (3)H-deprenyl autoradiographies were carried out on frozen brain sections from three AD patients and one healthy control. (3)H-THK5117 showed a distinct laminar cortical binding similar to (3)H-deprenyl autoradiography, with an extensive binding in the superficial and deep layers of the temporal neocortices, whereas the middle frontal gyrus showed an even binding throughout the layers...
April 4, 2017: Scientific Reports
Martin Schain, William Charles Kreisl
The potential for positron emission tomography (PET) to detect neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [(11)C]PK(R)-11195 for the 18-kDa translocator protein (TSPO) and [(11)C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid...
March 2017: Current Neurology and Neuroscience Reports
Rajeev K Singla, Luciana Scotti, Ashok K Dubey
BACKGROUND: Ursolic acid, a bioactive pentacyclic triterpenoid had been evaluated for its interaction with the neurological targets associated with antidepressant drugs. Current study was to mechanistically analyze the probable site of action for ursolic acid on the target proteins. METHODS: Ursolic acid has been docked with monoamine oxidase isoforms: MAO-A and MAO-B, LeuT (homologue of SERT, NET, DAT) and Human C-terminal CAP1 using GRIP docking methodology. RESULTS: Results revealed its non-selective antidepressant action with strong binding affinity towards LeuT and MAO-A proteins, which was found to be comparable with the reference ligands like chlorgyline, clomipramine, sertraline and deprenyl / selegiline...
December 29, 2016: Current Neuropharmacology
Philippe De Deurwaerdère, Claudia Binda, Rémi Corne, Cosima Leone, Aurora Valeri, Massimo Valoti, Rona R Ramsay, Yagamare Fall, José Marco-Contelles
The regulation of brain monoamine levels is paramount for cognitive functions, and the monoamine oxidase (MAO A and B) enzymes play a central role in these processes. The aim of this study was to evaluate whether the procognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both of the classic MAO A and MAO B inhibitors, clorgyline and l-deprenyl, respectively...
December 30, 2016: ACS Chemical Neuroscience
Maria Lalkovicova, Frantiska Horvathova, Igor Sulla, Jozef Mihalik, Viera Danielisova
We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD (p <0.05) in the cortex (0.74 ± 0.03; 0.31 ± 0.02), striatum (0.75 ± 0.02; 0.27 ± 0.03) and CA1 region of the hippocampus (0.75 ± 0.02; 0.29 ± 0.03) compared to the control (0.53 ± 0.02; 0.15 ± 0.02), but reduced (p <0...
January 2017: General Physiology and Biophysics
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
J Knoll, I Miklya
AIMS: The first longevity study demonstrating that rats treated with the MAO-B inhibitory dose of (-)-deprenyl (0.25mg/kg) lived significantly longer than their saline-treated peers was published in 1988, and corroborated in many papers. The recent findings that (-)-deprenyl is primarily a PEA-derived synthetic catecholaminergic activity enhancer substance; (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) is a tryptamine-derived synthetic enhancer substance, initiated our first longevity study on rats with low enhancer doses of (-)-deprenyl and BPAP to test the enhancer effect's role in life extension...
December 15, 2016: Life Sciences
Stefan Sturm, Anton Forsberg, Stephane Nave, Per Stenkrona, Nicholas Seneca, Andrea Varrone, Robert A Comley, Patrik Fazio, Candice Jamois, Ryuji Nakao, Zbigniew Ejduk, Nabil Al-Tawil, Ulrika Akenine, Christer Halldin, Niels Andreasen, Benedicte Ricci
PURPOSE: In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD...
March 2017: European Journal of Nuclear Medicine and Molecular Imaging
Rona R Ramsay, Magdalena Majekova, Milagros Medina, Massimo Valoti
HIGHLIGHTS Compounds that interact with multiple targets but minimally with the cytochrome P450 system (CYP) address the many factors leading to neurodegeneration.Acetyl- and Butyryl-cholineEsterases (AChE, BChE) and Monoamine Oxidases A/B (MAO A, MAO B) are targets for Multi-Target Designed Ligands (MTDL).ASS234 is an irreversible inhibitor of MAO A >MAO B and has micromolar potency against the cholinesterases.ASS234 is a poor CYP substrate in human liver, yielding the depropargylated metabolite.SMe1EC2, a stobadine derivative, showed high radical scavenging property, in vitro and in vivo giving protection in head trauma and diabetic damage of endothelium...
2016: Frontiers in Neuroscience
Nour K Majbour, Nishant N Vaikath, Paolo Eusebi, Davide Chiasserini, Mustafa Ardah, Shiji Varghese, M Emdadul Haque, Takahiko Tokuda, Peggy Auinger, Paolo Calabresi, Lucilla Parnetti, Omar M A El-Agnaf
BACKGROUND: Parkinson's disease (PD) diagnosis is mainly based on clinical criteria, with a high risk of misdiagnosis. The identification of reliable biomarkers for disease diagnosis and progression has a key role for developing disease-modifying therapies. In this article, we investigated the longitudinal changes of CSF α-synuclein species in early PD patients and explored the potential use of these species as surrogate biomarkers for PD progression. METHODS: We used our newly developed enzyme-linked immunosorbent assay systems for measuring different forms of α-synuclein, such as oligomeric-α-synuclein, phosphorylated-α-synuclein at serine 129, or total-α-synuclein in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study cohort (n = 121)...
October 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Františka Horváthová, Viera Danielisová, Iveta Domoráková, Peter Solár, Silvia Rybárová, Ingrid Hodorová, Jozef Mihalik
The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the activity and localization of superoxide dismutases (SODs) and catalase (CAT) in rat testis. After 30 days of intraperitoneal administration of either saline (control) or R-(-)-deprenyl dissolved in saline at concentrations of 0.0025mg/kg (low dose of deprenyl, LDD) or 0.25mg/kg (high dose of deprenyl, HDD), males were killed by thiopental, and their testes were collected. We found that deprenyl administration significantly increased the activity of antioxidant enzymes, and this effect varied by dosage...
October 5, 2016: European Journal of Pharmacology
Daniela Schulz, Fritz A Henn, David Petri, Joseph P Huston
Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule...
August 4, 2016: Neuroscience
Najla O Zarmouh, Samia S Messeha, Faisel M Elshami, Karam F A Soliman
Monoamine oxidases inhibitors (MAOIs) are effective therapeutic drugs for managing Parkinson's disease (PD) and depression. However, their irreversibility may lead to rare but serious side effects. As finding safer and reversible MAOIs is our target, we characterized the recombinant human (h) MAO-A and MAO-B inhibition potentials of two common natural isoflavones, genistein (GST) and daidzein (DZ) using luminescence assay. The results obtained showed that DZ exhibits partial to no inhibition of the isozymes examined while GST inhibited hMAO-B (IC50 of 6...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Anna Lesniak, Mikko Aarnio, Anna Jonsson, Thomas Norberg, Fred Nyberg, Torsten Gordh
AIMS: d-deprenyl is a useful positron emission tomography tracer for visualization of inflammatory processes. Studies with [(11)C]-d-deprenyl showed robust uptake in peripheral painful sites of patients with rheumatoid arthritis or chronic whiplash injury. The mechanism of preferential d-deprenyl uptake is not yet known, but the existence of a specific binding site was proposed. Thus, in the present study, we sought to identify the binding site for d-deprenyl and verify the hypothesis about the possibility of monoamine oxidase enzymes as major targets for this molecule...
May 1, 2016: Life Sciences
Elena Rodriguez-Vieitez, Stephen F Carter, Konstantinos Chiotis, Laure Saint-Aubert, Antoine Leuzy, Michael Schöll, Ove Almkvist, Anders Wall, Bengt Långström, Agneta Nordberg
UNLABELLED: The PET tracer (11)C-deuterium-L-deprenyl ((11)C-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase (11)C-DED and (11)C-Pittsburgh compound B ((11)C-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which (11)C-DED binding is influenced by brain perfusion was investigated. METHODS: (11)C-DED, (11)C-PiB, and (18)F-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16)...
July 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Elena Rodriguez-Vieitez, Laure Saint-Aubert, Stephen F Carter, Ove Almkvist, Karim Farid, Michael Schöll, Konstantinos Chiotis, Steinunn Thordardottir, Caroline Graff, Anders Wall, Bengt Långström, Agneta Nordberg
Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer (11)C-deuterium-L-deprenyl), fibrillar amyloid-β plaque deposition ((11)C-Pittsburgh compound B), and glucose metabolism ((18)F-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms...
March 2016: Brain: a Journal of Neurology
Pablo Buccino, Ingrid Kreimerman, Kevin Zirbesegger, Williams Porcal, Eduardo Savio, Henry Engler
Two (11)C-labelled PET tracers, (R)-N-[(11)C]methyl-N-(3,3-dideuteropropargyl)-1-phenylpropan-2-amine ([(11)C]L-deprenyl-D2, [(11)C]DED) and (S)-N-[(11)C]methyl-N-propargyl-1-phenylpropan-2-amine ([(11)C]D-deprenyl, [(11)C]DDE) were synthesised. One step N-alkylation with [(11)C]MeI or [(11)C]MeOTf was performed using the automated platform TRACERlab® FX-C Pro. The labelled products were obtained with (37±15)% (n=10) (end of synthesis, decay corrected from [(11)C]MeI) radiochemical yields from [(11)C]MeI after 38±3min synthesis time...
April 2016: Applied Radiation and Isotopes
Geng Chen, Sheng Luo
The multilevel item response theory (MLIRT) models have been increasingly used in longitudinal clinical studies that collect multiple outcomes. The MLIRT models account for all the information from multiple longitudinal outcomes of mixed types (e.g., continuous, binary, and ordinal) and can provide valid inference for the overall treatment effects. However, the continuous outcomes and the random effects in the MLIRT models are often assumed to be normally distributed. The normality assumption can sometimes be unrealistic and thus may produce misleading results...
July 2016: Biometrical Journal. Biometrische Zeitschrift
Hyong Woo Choi, Miaoying Tian, Murli Manohar, Maged M Harraz, Sang-Wook Park, Frank C Schroeder, Solomon H Snyder, Daniel F Klessig
The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA...
2015: PloS One
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