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https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#1
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079433/pet-imaging-of-cannabinoid-type-2-receptors-with-11-c-a-836339-did-not-evidence-changes-following-neuroinflammation-in-rats
#2
Geraldine Pottier, Vanessa Gómez-Vallejo, Daniel Padro, Raphaël Boisgard, Frédéric Dollé, Jordi Llop, Alexandra Winkeler, Abraham Martín
Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [(11)C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28077511/altered-connectivity-and-synapse-maturation-of-the-hippocampal-mossy-fiber-pathway-in-a-mouse-model-of-the-fragile-x-syndrome
#3
F Scharkowski, Michael Frotscher, David Lutz, Martin Korte, Kristin Michaelsen-Preusse
The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons...
January 10, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#4
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28071892/transient-adenosine-release-is-modulated-by-nmda-and-gabab-receptors
#5
Michael D Nguyen, Ying Wang, Mallikarjunarao Ganesana, B Jill Venton
Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1 and A2a receptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen...
January 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#6
Jie Li, Mark L Baccei
: It is well-established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared to skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared to pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn (SDH) neurons process sensory input from muscle vs...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28063882/mice-lacking-grip1-2-show-increased-social-interactions-and-enhanced-phosphorylation-at-glua2-s880
#7
Mei Han, Rebeca Mejias, Shu-Ling Chiu, Rebecca Rose, Abby Adamczyk, Richard Huganir, Tao Wang
Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background...
January 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28059046/long-term-effects-of-aripiprazole-exposure-on-monoaminergic-and-glutamatergic-receptor-subtypes-comparison-with-cariprazine
#8
Yong Kee Choi, Nika Adham, Béla Kiss, István Gyertyán, Frank I Tarazi
OBJECTIVE: This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data. METHODS: Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu-M), caudate-putamen lateral (CPu-L), hippocampal CA1 (HIPP-CA1) and CA3 (HIPP-CA3) regions, and the entorhinal cortex (EC)...
January 6, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/28058675/neuropeptide-cycloprolylglycine-is-an-endogenous-positive-modulator-of-ampa-receptors
#9
T A Gudasheva, V V Grigoriev, K N Koliasnikova, V L Zamoyski, S B Seredenin
We have previously shown that neuropeptide cycloprolylglycine (CPG) increases the content of brain-derived neurotrophic factor (BDNF) in the culture of neuronal cells under normal conditions and in pathology. This is the first study to show that CPG at a physiological concentration of 10(-6) M significantly enhances the transmembrane AMPA currents in rat cerebellar Purkinje cells. Thus, CPG is a positive endogenous modulator of AMPA receptors. It was assumed that the neuropsychotropic effects of CPG are implemented as a result of BDNF accumulation after the activation of AMPA receptors by this neuropeptide...
November 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28057533/presynaptic-pick1-facilitates-trafficking-of-ampa-receptors-between-active-zone-and-synaptic-vesicle-pool
#10
C Haglerød, S Hussain, Y Nakamura, J Xia, F M Haug, O P Ottersen, J M Henley, S Davanger
Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28054099/feeding-modulatory-effects-of-mu-opioids-in-the-medial-prefrontal-cortex-a-review-of-recent-findings-and-comparison-to-opioid-actions-in-the-nucleus-accumbens
#11
REVIEW
Ryan A Selleck, Brian A Baldo
RATIONALE: Whereas reward-modulatory opioid actions have been intensively studied in subcortical sites such as the nucleus accumbens (Acb), the role of cortical opioid transmission has received comparatively little attention. OBJECTIVES: The objective of this study is to describe recent findings on the motivational actions of opioids in the prefrontal cortex (PFC), emphasizing studies of food motivation and ingestion. PFC-based opioid effects will be compared/contrasted to those elicited from the Acb, to glean possible common functional principles...
January 4, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28052116/functional-maturation-of-human-stem-cell-derived-neurons-in-long-term-cultures
#12
Rebecca S Lam, Felix M Töpfer, Phillip G Wood, Volker Busskamp, Ernst Bamberg
Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28045462/hippocampal-encoding-of-interoceptive-context-during-fear-conditioning
#13
S-W Yoo, M Bae, L B Tovar-Y-Romo, N J Haughey
Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28045133/calpain-dependent-disruption-of-nucleo-cytoplasmic-transport-in-als-motor-neurons
#14
Takenari Yamashita, Hitoshi Aizawa, Sayaka Teramoto, Megumi Akamatsu, Shin Kwak
Nuclear dysfunction in motor neurons has been hypothesized to be a principal cause of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we investigated the mechanism by which the nuclear pore complex (NPC) is disrupted in dying motor neurons in a mechanistic ALS mouse model (adenosine deaminase acting on RNA 2 (ADAR2) conditional knockout (AR2) mice) and in ALS patients. We showed that nucleoporins (Nups) that constituted the NPC were cleaved by activated calpain via a Ca(2+)-permeable AMPA receptor-mediated mechanism in dying motor neurons lacking ADAR2 expression in AR2 mice...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043916/ketamine-accelerates-fear-extinction-via-mtorc1-signaling
#15
Matthew J Girgenti, Sriparna Ghosal, Dora LoPresto, Jane R Taylor, Ronald S Duman
Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28043063/investigation-of-neuronal-auto-antibodies-in-systemic-lupus-erythematosus-patients-with-epilepsy
#16
Zerrin Karaaslan, Esme Ekizoğlu, Pınar Tektürk, Ece Erdağ, Erdem Tüzün, Nerses Bebek, Candan Gürses, Betül Baykan
PURPOSE: Epilepsy is an important feature for neuropsychiatric involvement in systemic lupus erythematosus (SLE) with unknown mechanism. Our aim was to investigate the presence of neuronal auto-antibodies (NAbs) in neuropsychiatric SLE (NPSLE). METHODS: Eighteen SLE patients (17 females, 1 male) experiencing recurrent seizures were enrolled to this study. Their clinical characteristics, EEG and MRI findings and follow-up information were evaluated from their files...
December 14, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28041893/effects-of-methylmercury-on-spinal-cord-afferents-and-efferents-a-review
#17
Alexandra Colón-Rodríguez, Heidi E Hannon, William D Atchison
Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca(2+)-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier...
December 29, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/28038388/evaluation-of-perampanel-in-patients-with-intellectual-disability-and-epilepsy
#18
Francesca M Snoeijen-Schouwenaars, Jans S van Ool, In Y Tan, Helenius J Schelhaas, Marian H J M Majoie
INTRODUCTION: Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population...
December 27, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28034784/altered-ampa-receptor-expression-plays-an-important-role-in-inducing-bidirectional-synaptic-plasticity-during-contextual-fear-memory-reconsolidation
#19
Subhrajit Bhattacharya, Whitney Kimble, Manal Buabeid, Dwipayan Bhattacharya, Jenna Bloemer, Ahmad Alhowail, Miranda Reed, Muralikrishnan Dhanasekaran, Martha Escobar, Vishnu Suppiramaniam
Retrieval of a memory appears to render it unstable until the memory is once again re-stabilized or reconsolidated. Although the occurrence and consequences of reconsolidation have received much attention in recent years, the specific mechanisms that underlie the process of reconsolidation have not been fully described. Here, we present the first electrophysiological model of the synaptic plasticity changes underlying the different stages of reconsolidation of a conditioned fear memory. In this model, retrieval of a fear memory results in immediate but transient alterations in synaptic plasticity, mediated by modified expression of the glutamate receptor subunits GluA1 and GluA2 in the hippocampus of rodents...
December 26, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28030754/tonotopic-action-potential-tuning-of-maturing-auditory-neurons-through-endogenous-atp
#20
Saša Jovanovic, Tamara Radulovic, Claudio Coddou, Beatrice Dietz, Jana Nerlich, Stanko S Stojilkovic, Rudolf Rübsamen, Ivan Milenkovic
KEY POINTS: Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map. In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell-specific and tonotopically-determined manner...
November 7, 2016: Journal of Physiology
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