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https://www.readbyqxmd.com/read/29346545/influence-of-nicotine-metabolism-ratio-on-11c-phno-pet-binding-in-tobacco-smokers
#1
Patricia Di Ciano, Rachel F Tyndale, Esmaeil Mansouri, Christian S Hendershot, Alan A Wilson, Dina Lagzdins, Sylvain Houle, Isabelle Boileau, Bernard Le Foll
Background: Identifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), affects multiple aspects of nicotine dependence. Fast nicotine metabolizers (FM) tend to smoke more, experience more withdrawal and craving and have lower cessation rates as compared to slow metabolizers (SM). The NMR predicts treatment response, and differences in brain activation between FM and SM have been reported in fMRI studies...
January 13, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#2
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29343749/testosterone-boosts-physical-activity-in-male-mice-via-dopaminergic-pathways
#3
Ferran Jardí, Michaël R Laurent, Nari Kim, Rougin Khalil, Dimitri De Bundel, Ann Van Eeckhaut, Lawrence Van Helleputte, Ludo Deboel, Vanessa Dubois, Dieter Schollaert, Brigitte Decallonne, Geert Carmeliet, Ludo Van den Bosch, Rudi D'Hooge, Frank Claessens, Dirk Vanderschueren
Low testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of "low free T". Our results clearly show a fast and dramatic action of T stimulating wheel running, which is not explained by its action on muscle, as evidenced by neuromuscular studies and in a muscle-specific conditional ARKO mouse model...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343158/placebo-effects-in-traumatic-brain-injury
#4
Ginger Polich, Mary Alexis Iaccarino, Ted J Kaptchuk, Leon Morales-Quezada, Ross Zafonte
In recent years, several randomized controlled trials evaluating pharmaceutical treatments for traumatic brain injury (TBI) have failed to demonstrate efficacy over placebo, with both active and placebo arms improving at comparable rates. These findings could be viewed in opposing ways, suggesting on the one hand failure of the tested outcome, but representing on the other, evidence of robust placebo effects in TBI. In this article, we examine several of the primary psychological processes driving placebo effects (verbal suggestion, cognitive re-framing, interpersonal interactions, conditioning, therapeutic alliance, anxiety reduction) as well as placebo neurobiology (top-down cortical regulation, reward system activation, dopaminergic and serotonergic neurotransmission)...
January 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29342497/non-antipsychotic-catecholaminergic-drugs-for-antipsychotic-induced-tardive-dyskinesia
#5
REVIEW
Hany G El-Sayeh, John Rathbone, Karla Soares-Weiser, Hanna Bergman
BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: 1...
January 18, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29339319/treatment-with-the-noradrenaline-re-uptake-inhibitor-atomoxetine-alone-and-in-combination-with-the-%C3%AE-2-adrenoceptor-antagonist-idazoxan-attenuates-loss-of-dopamine-and-associated-motor-deficits-in-the-lps-inflammatory-rat-model-of-parkinson-s-disease
#6
Justin D Yssel, Eoin O'Neill, Yvonne M Nolan, Thomas J Connor, Andrew Harkin
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment...
January 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29339106/safinamide-a-new-hope-for-parkinson-s-disease
#7
REVIEW
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
January 12, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29339100/genetic-variation-in-the-dopamine-system-influences-intervention-outcome-in-children-with-cerebral-palsy
#8
Rochellys Diaz Heijtz, Rita Almeida, Ann Christin Eliasson, Hans Forssberg
BACKGROUND: There is large variation in treatment responses in children with cerebral palsy. Experimental and clinical results suggest that dopamine neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are involved in motor learning and plasticity, which are key factors in modern habilitation success. We examined whether naturally occurring variations in dopamine and BDNF genes influenced the treatment outcomes. METHODS: Thirty-three children (18-60months of age) with spastic unilateral cerebral palsy were enrolled in the study...
January 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#9
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29337144/early-activation-of-egr-1-promotes-neuroinflammation-and-dopaminergic-neurodegeneration-in-an-experimental-model-of-parkinson-s-disease
#10
Qing Yu, Qiaoying Huang, Xiaoxiao Du, Shao Xu, Mingtao Li, Shanshan Ma
The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction of Egr-1 in the SNpc but not in the striatum...
January 11, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29336905/getting-a-good-night-sleep-the-importance-of-recognizing-and-treating-nocturnal-hypokinesia-in-parkinson-s-disease
#11
REVIEW
Roongroj Bhidayasiri, Claudia Trenkwalder
When Parkinson's disease (PD) patients are asked about the quality of their sleep, their answers are dominated by difficulties associated with impaired mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70% of PD patients, and contributes to poor sleep quality, and increased carer burden. Here we explore four areas of nocturnal hypokinesia that are relevant to clinical practice, namely: manifestations and definition; clinical assessment and objective monitoring; etiologies and contributing factors; and evidence-based therapeutic approaches...
January 5, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29335159/repeated-domperidone-treatment-modulates-pulmonary-cytokines-in-lps-induced-acute-lung-injury-in-mice
#12
Talita Rossetto Barreto, Carolina Costola-de-Souza, Rafael Oliveira Margatho, Nicolle Queiroz-Hazarbassanov, Sandra Campos Rodrigues, Luciano Freitas Felício, João Palermo-Neto, Adriano Zager
The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We investigated the effects of repeated Domperidone treatment in a model of Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice were treated with either Vehicle or Domperidone for 5days, and challenged intranasally with LPS in the following day. The behavior of mice was analyzed in the open field and elevated plus-maze test before and 24h after LPS challenge. The bronchoalveolar lavage fluid, blood and lung tissue were collected 24h and 48h after LPS challenge...
January 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29334687/cognitive-deficits-in-methamphetamine-users-how-strong-is-the-evidence
#13
Lisa Proebstl, Felicia Kamp, Gabi Koller, Michael Soyka
Methamphetamine use has spread in many European countries and the United States. The current review provides a summary and critical analysis of research on cognitive deficits associated with methamphetamine, also known as "crystal meth." The literature search performed for this review led us to the hypothesis that methamphetamine use is associated with persistent changes in brain metabolism that result in various impairments, such as deficits in memory, attention, and concentration. The dopaminergic system in particular seems to be affected...
January 15, 2018: Pharmacopsychiatry
https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#14
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#15
Jong Hoon Won, Seok Kyun Kim, In Chul Shin, Hae Chan Ha, Ji Min Jang, Moon Jung Back, Dae Kyong Kim
Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29327219/pharmacological-insights-into-the-use-of-apomorphine-in-parkinson-s-disease-clinical-relevance
#16
REVIEW
Manon Auffret, Sophie Drapier, Marc Vérin
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic...
January 11, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29327204/neuroprotective-effects-of-filgrastim-in-rotenone-induced-parkinson-s-disease-in-rats-insights-into-its-anti-inflammatory-neurotrophic-and-antiapoptotic-effects
#17
Mariama S Azmy, Esther T Menze, Reem N El-Naga, Mariane G Tadros
All current treatments of Parkinson's disease (PD) focus on enhancing the dopaminergic effects and providing symptomatic relief; however, they cannot delay the disease progression. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor, demonstrated neuroprotection in many neurodegenerative and neurological diseases. This study aimed to assess the neuroprotective effects of filgrastim in rotenone-induced rat model of PD and investigate the potential underlying mechanisms of filgrastim actions...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29325757/the-role-of-fatty-acids-and-their-endocannabinoid-like-derivatives-in-the-molecular-regulation-of-appetite
#18
REVIEW
Renger F Witkamp
Intake, absorption and synthesis of fatty acids, including those produced by the intestinal microbiota are tightly monitored via specific receptors and, indirectly through their conversion into a variety of signalling molecules. The resulting information is integrated and translated to different physiological processes, including the regulation of appetite and satiation. Direct chemosensing of fatty acids takes place via interaction with free fatty acid (FFA) and other receptors. These are present in the oronasal cavity and along the entire gastrointestinal tract, in various other tissues, and, for some receptors also in brain...
January 8, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29323027/micrornas-in-parkinson-s-disease-and-emerging-therapeutic-targets
#19
REVIEW
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29315936/biosynthesis-of-bioactive-diterpenoids-in-the-medicinal-plant-vitex-agnus-castus
#20
Allison Maree Heskes, Tamil C M Sundram, Berin Alain Boughton, Niels Bjerg Jensen, Nikolaj Lervad Hansen, Christoph Crocoll, Federico Cozzi, Simon Rasmussen, Britta Hamberger, Björn Hamberger, Dan Staerk, Birger Lindberg Møller, Irini Pateraki
Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such holds potential as a rich source of new dopaminergic drugs...
January 8, 2018: Plant Journal: for Cell and Molecular Biology
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