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https://www.readbyqxmd.com/read/28231626/default-mode-network-deactivation-to-smoking-cue-relative-to-food-cue-predicts-treatment-outcome-in-nicotine-use-disorder
#1
Claire E Wilcox, Eric D Claus, Vince D Calhoun, Srinivas Rachakonda, Rae A Littlewood, Jessica Mickey, Pamela B Arenella, Natalie Goodreau, Kent E Hutchison
Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo...
February 23, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28231468/parkinson-sac-domain-mutation-in-synaptojanin-1-impairs-clathrin-uncoating-at-synapses-and-triggers-dystrophic-changes-in-dopaminergic-axons
#2
Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J McCartney, Heather Wheeler, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Timothy A Ryan, Pietro De Camilli
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1's 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231336/comparison-of-neurological-health-outcomes-between-two-adolescent-cohorts-exposed-to-pesticides-in-egypt
#3
Ahmed A Ismail, Matthew R Bonner, Olfat Hendy, Gaafar Abdel Rasoul, Kai Wang, James R Olson, Diane S Rohlman
Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds...
2017: PloS One
https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#4
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230848/computational-approaches-to-fmri-analysis
#5
Jonathan D Cohen, Nathaniel Daw, Barbara Engelhardt, Uri Hasson, Kai Li, Yael Niv, Kenneth A Norman, Jonathan Pillow, Peter J Ramadge, Nicholas B Turk-Browne, Theodore L Willke
Analysis methods in cognitive neuroscience have not always matched the richness of fMRI data. Early methods focused on estimating neural activity within individual voxels or regions, averaged over trials or blocks and modeled separately in each participant. This approach mostly neglected the distributed nature of neural representations over voxels, the continuous dynamics of neural activity during tasks, the statistical benefits of performing joint inference over multiple participants and the value of using predictive models to constrain analysis...
February 23, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28230845/dynamic-models-of-large-scale-brain-activity
#6
REVIEW
Michael Breakspear
Movement, cognition and perception arise from the collective activity of neurons within cortical circuits and across large-scale systems of the brain. While the causes of single neuron spikes have been understood for decades, the processes that support collective neural behavior in large-scale cortical systems are less clear and have been at times the subject of contention. Modeling large-scale brain activity with nonlinear dynamical systems theory allows the integration of experimental data from multiple modalities into a common framework that facilitates prediction, testing and possible refutation...
February 23, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28230841/magnetoencephalography-for-brain-electrophysiology-and-imaging
#7
REVIEW
Sylvain Baillet
We review the aspects that uniquely characterize magnetoencephalography (MEG) among the techniques available to explore and resolve brain function and dysfunction. While emphasizing its specific strengths in terms of millisecond source imaging, we also identify and discuss current practical challenges, in particular in signal extraction and interpretation. We also take issue with some perceived disadvantages of MEG, including the misconception that the technique is redundant with electroencephalography. Overall, MEG contributes uniquely to our deeper comprehension of both regional and large-scale brain dynamics: from the functions of neural oscillations and the nature of event-related brain activation, to the mechanisms of functional connectivity between regions and the emergence of modes of network communication in brain systems...
February 23, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28230741/high-frequency-repetitive-transcranial-magnetic-stimulation-rtms-improves-functional-recovery-by-enhancing-neurogenesis-and-activating-bdnf-trkb-signaling-in-ischemic-rats
#8
Jing Luo, Haiqing Zheng, Liying Zhang, Qingjie Zhang, Lili Li, Zhong Pei, Xiquan Hu
Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats...
February 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230651/hypoxia-induces-internalization-of-%C3%AE%C2%BA-opioid-receptor
#9
Chunhua Xi, Xuan Liang, Chunhua Chen, Hasan Babazada, Tianzuo Li, Renyu Liu
BACKGROUND: It has been demonstrated that κ-opioid receptor agonists can reduce hypoxia-ischemia brain injury in animal models. However, it is unclear how the κ-opioid receptor responds to hypoxia-ischemia. In the current study, the authors used an in vitro model of oxygen-glucose deprivation and reoxygenation to explore how κ-opioid receptors respond to hypoxia and reoxygenation. METHODS: Mouse neuroblastoma Neuro2A cells were stably transfected with mouse κ-opioid receptor-tdTomato fusion protein or Flag-tagged mouse κ-opioid receptor, divided into several groups (n = 6 to 12), and used to investigate the κ-opioid receptor movement...
February 23, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28230635/valproic-acid-modulates-platelet-and-coagulation-function-ex-vivo
#10
Ted Bambakidis, Simone E Dekker, Ihab Halaweish, Baoling Liu, Vahagn C Nikolian, Patrick E Georgoff, Patryk Piascik, Yongqing Li, Martin Sillesen, Hasan B Alam
Trauma-induced coagulopathy is associated with adverse patient outcome. Animal models demonstrate that histone deacetylase inhibitors, such as valproic acid (VPA), improve survival following injury. While in-vivo data suggest that improved survival may in part be because of an attenuation of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype. We thus conducted an ex-vivo experiment to determine if VPA has an effect on coagulation and platelet function...
February 21, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28230352/disease-modifying-effects-of-m1-muscarinic-acetylcholine-receptor-activation-in-an-alzheimer-s-disease-mouse-model
#11
Evan P Lebois, Jason P Schroeder, Thomas J Esparza, Thomas M Bridges, Craig W Lindsley, P Jeffrey Conn, David L Brody, John Scott Daniels, Allan I Levey
Alzheimer's Disease (AD) is the leading cause of dementia worldwide and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months)...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28230291/therapeutic-potentials-of-bdnf-trkb-in-breast-cancer-current-status-and-perspectives
#12
Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A Ferns, Alireza Pasdar, Amir Avan
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB and the p75(NTR) death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230174/a-hydrophobic-patch-surrounding-trp154-in-human-neuroserpin-controls-the-helix-f-dynamics-with-implications-in-inhibition-and-aggregation
#13
Mohammad Farhan Ali, Abhinav Kaushik, Charu Kapil, Dinesh Gupta, Mohamad Aman Jairajpuri
Neuroserpin (NS) mediated inhibition of tissue-type plasminogen activator (tPA) is important for brain development, synapse formation and memory. Aberrations in helix F and β-sheet A movement during inhibition can directly lead to epilepsy or dementia. Conserved W154 residue in a hydrophobic patch between helix F and β-sheet A is ideally placed to control their movement during inhibition. Molecular Dynamics (MD) simulation on wild type (WT) NS and its two variants (W154A and W154P) demonstrated partial deformation in helix F and conformational differences in strands 1A and 2A only in W154P...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230070/an-fmri-compatible-force-measurement-system-for-the-evaluation-of-the-neural-correlates-of-step-initiation
#14
Andrea Cristina de Lima-Pardini, Raymundo Machado de Azevedo Neto, Daniel Boari Coelho, Catarina Costa Boffino, Sukhwinder S Shergill, Carolina de Oliveira Souza, Rachael Brant, Egberto Reis Barbosa, Ellison Fernando Cardoso, Luis Augusto Teixeira, Rajal G Cohen, Fay Bahling Horak, Edson Amaro
Knowledge of brain correlates of postural control is limited by the technical difficulties in performing controlled experiments with currently available neuroimaging methods. Here we present a system that allows the measurement of anticipatory postural adjustment of human legs to be synchronized with the acquisition of functional magnetic resonance imaging data. The device is composed of Magnetic Resonance Imaging (MRI) compatible force sensors able to measure the level of force applied by both feet. We tested the device in a group of healthy young subjects and a group of elderly subjects with Parkinson's disease using an event-related functional MRI (fMRI) experiment design...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230058/macrophage-migration-inhibitory-factor-is-subjected-to-glucose-modification-and-oxidation-in-alzheimer-s-disease
#15
Omar Kassaar, Marta Pereira Morais, Suying Xu, Emily L Adam, Rosemary C Chamberlain, Bryony Jenkins, Tony James, Paul T Francis, Stephen Ward, Robert J Williams, Jean van den Elsen
Glucose and glucose metabolites are able to adversely modify proteins through a non-enzymatic reaction called glycation, which is associated with the pathology of Alzheimer's Disease (AD) and is a characteristic of the hyperglycaemia induced by diabetes. However, the precise protein glycation profile that characterises AD is poorly defined and the molecular link between hyperglycaemia and AD is unknown. In this study, we define an early glycation profile of human brain using fluorescent phenylboronate gel electrophoresis and identify early glycation and oxidation of macrophage migration inhibitory factor (MIF) in AD brain...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229935/mice-deficient-in-l-12-15-lipoxygenase-show-increased-vulnerability-to-3-nitropropionic-acid-neurotoxicity
#16
Yan He, Rita C Akumuo, Yuan Yang, Sandra J Hewett
Considerable evidence supports a contributory role for leukocyte-type 12/15 Lipoxygenase (L-12/15 LO) in mediating hippocampal and cortical neuronal injury in models of Alzheimer's disease and stroke. Whether L-12/15 LO contributes to neuronal injury in a model of Huntington's disease (HD) has yet to be determined. HD is characterized by marked striatal neuronal loss, which can be mimicked in humans and animals by inhibition of mitochondrial complex II using 3-Nitropropionic acid (3-NP). Herein, we compared histological and behavioral outcomes between mice that were wild-type or null for L-12/15 LO following systemic injection of 3NP...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229913/increased-risk-of-developing-schizophrenia-in-animals-exposed-to-cigarette-smoke-during-the-gestational-period
#17
Alexandra I Zugno, Mariana B Oliveira, Gustavo A Mastella, Alexandra S A Heylmann, Lara Canever, Felipe D Pacheco, Louyse S Damazio, Sullivan A Citadin, Luiz Antonio de Lucca, Lutiana Roque Simões, Fernanda Malgarin, Josiane Budni, Tatiana Barichello, Patricia F Schuck, João Quevedo
Cigarette smoking during the prenatal period has been investigated as a causative factor of obstetric abnormalities, which lead to cognitive and behavioural changes associated with schizophrenia. The aim of this study was to investigate behaviour and AChE activity in brain structures in adult rats exposed to cigarette smoke during the prenatal period. Pregnant rats were divided into non-PCSE (non-prenatal cigarette smoke exposure) and PCSE (prenatal cigarette smoke exposure) groups. On post-natal day 60, the rats received saline or ketamine for 7days and were subjected to behavioural tasks...
February 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28229892/safety-and-efficacy-of-opicinumab-in-acute-optic-neuritis-renew-a-randomised-placebo-controlled-phase-2-trial
#18
Diego Cadavid, Laura Balcer, Steven Galetta, Orhan Aktas, Tjalf Ziemssen, Ludo Vanopdenbosch, Jette Frederiksen, Mark Skeen, Glenn J Jaffe, Helmut Butzkueven, Focke Ziemssen, Luca Massacesi, Yi Chai, Lei Xu, Stefanie Freeman
BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. METHODS: This randomised, double-blind, placebo-controlled, phase 2 study (RENEW) was done at 33 sites in Australia, Canada, and Europe in participants (aged 18-55 years) with a first unilateral acute optic neuritis episode within 28 days from study baseline...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28229459/differential-serotonergic-modulation-across-the-main-and-accessory-olfactory-bulbs
#19
Zhenbo Huang, Nicolas Thiebaud, Debra Ann Fadool
Mitral cells (MCs) contained in the main (MOB) and accessory (AOB) olfactory bulb have distinct intrinsic membrane properties but a comparison of the extent of neuromodulation across the two systems is not well explored. Herein, we investigated a widely-distributed CNS modulator, serotonin (5-HT), for its ability to modulate the biophysical properties of MCs across the MOB and AOB, using an in vitro, brain slice approach in postnatal 15-30 day mice. In the MOB, 5-HT elicited three types of responses in 93% of 180 cells tested...
February 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28229437/pharmacokinetic-modeling-of-11-c-flumazenil-kinetics-in-the-rat-brain
#20
Isadora Lopes Alves, David Vállez García, Andrea Parente, Janine Doorduin, Rudi Dierckx, Ana Maria Marques da Silva, Michel Koole, Antoon Willemsen, Ronald Boellaard
BACKGROUND: Preferred models for the pharmacokinetic analysis of [(11)C]flumazenil human studies have been previously established. However, direct translation of these models and settings to animal studies might be sub-optimal. Therefore, this study evaluates pharmacokinetic models for the quantification of [(11)C]flumazenil binding in the rat brain. Dynamic (60 min) [(11)C]flumazenil brain PET scans were performed in two groups of male Wistar rats (tracer dose (TD), n = 10 and pre-saturated (PS), n = 2)...
December 2017: EJNMMI Research
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