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https://www.readbyqxmd.com/read/29350251/pyramidal-cell-selective-glun1-knockout-causes-impairments-in-salience-attribution-and-related-eeg-activity
#1
Alexandra D Forrest, Jakyung Bang, Robert E Featherstone, Jonathan H Bloom, Matthew S Luminais, Rebecca V Zhang, Christopher R Gajewski, Mary F McMullen, Yuling Liang, Steven J Siegel
Schizophrenia is a disabling psychiatric disease characterized by symptoms including hallucinations, delusions, social withdrawal, loss of pleasure, and inappropriate affect. Although schizophrenia is marked by dysfunction in dopaminergic and glutamatergic signaling, it is not presently clear how these dysfunctions give rise to symptoms. The aberrant salience hypothesis of schizophrenia argues that abnormal attribution of motivational salience to stimuli is one of the main contributors to both positive and negative symptoms of schizophrenia...
January 19, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#2
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348266/dopamine-receptor-agonist-treatment-for-idiopathic-dystonia-a-reappraisal-in-humans-and-mice
#3
Xueliang Fan, Yuping Donsante, H A Jinnah, Ellen J Hess
Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general view that dopaminergic drugs are ineffective. However, there is little conclusive evidence to support or refute this assumption. Therefore, to assess the therapeutic potential of these compounds, we analyzed results from multiple trials of dopamine receptor agonists in patients with idiopathic dystonias and also tested the efficacy of dopamine receptor agonists in a mouse model of generalized dystonia...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29348190/pronounced-hyperactivity-cognitive-dysfunctions-and-bdnf-dysregulation-in-dopamine-transporter-knockout-rats
#4
Damiana Leo, Ilya Sukhanov, Francesca Zoratto, Placido Illiano, Lucia Caffino, Fabrizio Sanna, Giulia Messa, Marco Emanuele, Alessandro Esposito, Maria Dorofeikova, Evgeny A Budygin, Liudmila Mus, Evgenia E Efimova, Marco Niello, Stefano Espinoza, Tatyana D Sotnikova, Marius C Hoener, Gianni Laviola, Fabio Fumagalli, Walter Adriani, Raul R Gainetdinov
Dopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD). The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats (DAT-knockout, DAT-KO rats) in which the gene encoding the DAT has been disrupted by using zinc finger nuclease technology (ZFN)...
January 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29346545/influence-of-nicotine-metabolism-ratio-on-11c-phno-pet-binding-in-tobacco-smokers
#5
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/29346382/6-ohda-induced-dopaminergic-neurodegeneration-in-caenorhabditis-elegans-is-promoted-by-the-engulfment-pathway-and-inhibited-by-the-transthyretin-related-protein-ttr-33
#6
Sarah-Lena Offenburger, Xue Yan Ho, Theresa Tachie-Menson, Sean Coakley, Massimo A Hilliard, Anton Gartner
Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson's disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting Caenorhabditis elegans dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the transthyretin-related gene ttr-33. The only described C. elegans transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair...
January 2018: PLoS Genetics
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
#7
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/29344929/pla2g6-deficiency-in-zebrafish-leads-to-dopaminergic-cell-death-axonal-degeneration-increased-%C3%AE-synuclein-expression-and-defects-in-brain-functions-and-pathways
#8
Elena Sánchez, Luis J Azcona, Coro Paisán-Ruiz
This study aimed to gain insights into the pathophysiology underlying PLA2G6-associated neurodegeneration that is implicated in three different neurological disorders, suggesting that other, unknown genetic or environmental factors might contribute to its wide phenotypic expression. To accomplish this, we downregulated the function of pla2g6 in the zebrafish nervous system, performed parkinsonism-related phenotypic characterization, and determined the effects of gene regulation upon the loss of pla2g6 function by using RNA sequencing and downstream analyses...
January 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29344865/isolation-of-distinct-types-of-neurons-from-fresh-brain-tissue-using-laser-microdissection-in-combination-with-high-performance-liquid-chromatography-mass-spectrometry
#9
Luisa Aring, Simone Steinbach, Katrin Marcus, Caroline May
Humans age and the ageing process affects cells in all areas of the human body, including nerve cells within the brain. With advancing age there is also a rise in the probability of developing a neurodegenerative disorder such as, e.g., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, or Alzheimer's disease. In all these age-related neurodegenerative disorders, distinct neuron populations within specific brain regions are primarily affected. For example, Parkinson's disease is characterized by a slowly progressive degeneration of dopaminergic neurons in the substantia nigra whereas the entorhinal cortex is first affected in Alzheimer's disease...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343749/testosterone-boosts-physical-activity-in-male-mice-via-dopaminergic-pathways
#10
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
#11
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
#12
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/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#13
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339481/repetitive-aggressive-encounters-generate-a-long-lasting-internal-state-in-drosophila-melanogaster-males
#14
Yong-Kyu Kim, Mathias Saver, Jasper Simon, Clement F Kent, Lisha Shao, Mark Eddison, Pavan Agrawal, Michael Texada, James W Truman, Ulrike Heberlein
Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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
#15
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
#16
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
#17
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
#18
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/29337277/compensatory-dopaminergic-cholinergic-interactions-in-conflict-processing-evidence-from-patients-with-parkinson-s-disease
#19
REVIEW
Kamin Kim, Nicolaas I Bohnen, Martijn L T M Müller, Cindy Lustig
Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy controls, especially when associated with relatively preserved performance...
January 11, 2018: NeuroImage
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#20
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes are controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders...
January 11, 2018: Neuroscience
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