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https://www.readbyqxmd.com/read/29031144/senegenin-exerts-anti-depression-effect-in-mice-induced-by-chronic-un-predictable-mild-stress-via-inhibition-of-nf-%C3%AE%C2%BAb-regulating-nlrp3-signal-pathway
#1
Hongwei Li, Shiyi Lin, Tingting Qin, Hongyan Li, Zhanqiang Ma, Shiping Ma
Depressive disorder is a kind of affective disturbance disease. Emerging evidence has suggested that inflammation may contribute to the pathologic process of depressive disorder. Senegenin (SEN), a major bioactive constituent in Polygala tenuifolia Willd, has much bioactivity including anti-inflammatory and neuroprotection effects. However, the mechanism of its anti-depressant effect in mice remains unknown. This study aimed to explore the anti-depressant effects of SEN on behavioral changes and inflammatory responses in mice induced by chronic un-predictable mild stress (CUMS)...
October 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29031113/cross-sectional-and-longitudinal-small-animal-pet-shows-pre-and-post-synaptic-striatal-dopaminergic-deficits-in-an-animal-model-of-hiv
#2
Sanhita Sinharay, Dianne Lee, Swati Shah, Siva Muthusamy, Georgios Z Papadakis, Xiang Zhang, Dragan Maric, William C Reid, Dima A Hammoud
INTRODUCTION: In vivo imaging biomarkers of various HIV neuropathologies, including dopaminergic dysfunction, are still lacking. Towards developing dopaminergic biomarkers of brain involvement in HIV, we assessed the pre and postsynaptic components of the dopaminergic system in the HIV-1 transgenic rat (Tg), a well-characterized model of treated HIV+ patients, using small-animal PET imaging. METHODS: Fifteen to 18 month-old Tg and wild type (WT) rats were imaged with both [18F]-FP-CMT, a dopamine transporter (DAT) ligand (n=16), and [18F]-Fallypride, a D2/D3 dopamine receptor (D2/D3DR) ligand (n=16)...
August 31, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29031089/17%C3%AE-estradiol-regulates-the-rna-binding-protein-nova1-which-then-regulates-the-alternative-splicing-of-estrogen-receptor-%C3%AE-in-the-aging-female-rat-brain
#3
Cody L Shults, Caitlin B Dingwall, Chun K Kim, Elena Pinceti, Yathindar S Rao, Toni R Pak
Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens...
September 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29030219/local-infusion-of-ghrelin-into-the-lateral-amygdala-blocks-extinction-of-conditioned-taste-aversion-in-rats
#4
Ge Song, Qianqian Zhu, Fubing Han, Shuai Liu, Chenyang Zhao, Yu Zhou
Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. Our previous study showed that ghrelin locally infused into the lateral amygdala (LA) activates its receptor GHS-R1a and blocks acquisition of conditioned taste aversion (CTA) in rats. In this study, we further investigated the effect of ghrelin/GHS-R1a signaling on extinction of CTA. We found that local infusion of ghrelin (5μM, 0.5μl/side) into the LA not only interfered with CTA memory formation, but also the extinction of CTA memory...
October 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29030082/adx-47273-a-mglu5-receptor-positive-allosteric-modulator-attenuates-deficits-in-cognitive-flexibility-induced-by-withdrawal-from-binge-like-ethanol-exposure-in-rats
#5
Marta Marszalek-Grabska, Ewa Gibula-Bruzda, Anna Bodzon-Kulakowska, Piotr Suder, Kinga Gawel, Sylwia Talarek, Joanna Listos, Ewa Kędzierska, Wojciech Danysz, Jolanta H Kotlinska
Repeated exposure to and withdrawal from ethanol induces deficits in spatial reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors are implicated in synaptic plasticity and learning and memory. These receptors functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation of one type results in the activation of the other. We examined whether (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX-47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates deficits in reversal learning induced by withdrawal (11-13days) from 'binge-like' ethanol input (5...
October 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29029315/7-8-dihydroxyflavone-rescues-lead-induced-impairment-of-vesicular-release-a-novel-therapeutic-approach-for-lead-intoxicated-children
#6
Xiao-Lei Zhang, Jennifer L McGlothan, Omid Miry, Kirstie H Stansfield, Meredith K Loth, Patric K Stanton, Tomás R Guilarte
Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits.In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling...
October 4, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29029302/acute-kynurenine-challenge-disrupts-sleep-wake-architecture-and-impairs-contextual-memory-in-adult-rats
#7
Ana Pocivavsek, Annalisa M Baratta, Jessica A Mong, Shaun S Viechweg
Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality...
September 28, 2017: Sleep
https://www.readbyqxmd.com/read/29029017/region-specific-suppression-of-hypothalamic-responses-to-insulin-to-adapt-to-elevated-maternal-insulin-secretion-during-pregnancy
#8
S R Ladyman, D R Grattan
As part of the adaptation of maternal glucose regulation during pregnancy to ensure glucose provision to the fetus, maternal insulin concentrations become elevated. However, increased central actions of insulin, such as suppression of appetite, would be maladaptive during pregnancy. We hypothesized that central nervous system targets of insulin become less responsive during pregnancy to prevent overstimulation by the increased circulating insulin concentrations. To test this hypothesis, we have measured insulin-induced phosphorylation of Akt (pAkt) in specific hypothalamic nuclei as an index of hypothalamic insulin responsiveness...
September 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/29028939/serotonin-2a-receptor-signaling-underlies-lsd-induced-alteration-of-the-neural-response-to-dynamic-changes-in-music
#9
Frederick S Barrett, Katrin H Preller, Marcus Herdener, Petr Janata, Franz X Vollenweider
Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29028935/latent-profile-analysis-reveals-behavioral-and-brain-correlates-of-dopamine-cognition-associations
#10
Martin Lövdén, Nina Karalija, Micael Andersson, Anders Wåhlin, Jan Axelsson, Ylva Köhncke, Lars S Jonasson, Anna Rieckman, Goran Papenberg, Douglas D Garrett, Marc Guitart-Masip, Alireza Salami, Katrine Riklund, Lars Bäckman, Lars Nyberg, Ulman Lindenberger
Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with 11C-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed)...
September 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29028184/native-kcc2-interactome-reveals-pacsin1-as-a-critical-regulator-of-synaptic-inhibition
#11
Vivek Mahadevan, C Sahara Khademullah, Zahra Dargaei, Jonah Chevrier, Pavel Uvarov, Julian Kwan, Richard D Bagshaw, Tony Pawson, Andrew Emili, Yves De Koninck, Victor Anggono, Matti Airaksinen, Melanie A Woodin
KCC2 is a neuron-specific K(+)-Cl(-) cotransporter essential for establishing the Cl(-) gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-cav-channels
#12
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3)...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29027701/cellular-and-molecular-characterization-of-idh1-mutated-diffuse-low-grade-gliomas-reveals-tumor-heterogeneity-and-absence-of-egfr-pdgfr%C3%AE-activation
#13
S Azar, N Leventoux, C Ripoll, V Rigau, C Gozé, F Lorcy, L Bauchet, H Duffau, P O Guichet, B Rothhut, J P Hugnot
Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment...
October 13, 2017: Glia
https://www.readbyqxmd.com/read/29027610/risk-factors-for-and-incidence-of-seizures-in-metastatic-castration-resistant-prostate-cancer-a-real-world-retrospective-cohort-study
#14
Charles Dharmani, Machaon Bonafede, Andrew Krivoshik
BACKGROUND AND OBJECTIVE: This real-world study assessed the prevalence, risk factors for, and incidence of seizures in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC were selected from MarketScan Commercial and Medicare Supplemental Databases between 1 January 2009 and 31 July 2012. Prevalence of seizure risk factors were described separately and in combination with other risk factors. Seizure incidence was calculated overall and for each risk factor group...
October 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29027434/-protective-effect-of-notoginsenoside-r1-on-neuron-injury-induced-by-ogd-r-through-atf6-akt-signaling-pathway
#15
Qian-Ling Hou, Yan Wang, Ying-Bo Li, Xue-Lian Hu, Sha-Li Wang
Notoginsenoside R1(NGR1),a critical compound in traditional herb Panax notoginseng, is a kind of estrogen receptor agonist.It is reported to exhibit anti-apoptotic,anti-oxidative and anti-inflammatory properties activity, so it is widely used for treatment of various diseases.In order to investigate the potential neuroprotective effect of NGR1 in hypoxic-ischemic brain damage(HIBD), primary cortical neurons were used in this study to establish oxygen-glucose deprivation/reoxygenation(OGD/R) injury models. They were treated with NGR1 and estrogen receptor inhibitor ICI-182780 respectively, then the neuronal survival, cell membrane integrity and apoptosis were assessed by MTT assay,lactate dehydrogenase test(LDH) and Hoechst 33342 stain respectively, while the protein expression levels of ATF6α,p-Akt,Akt,Bax and Cleaved Caspase-3 were measured by Western blotting...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#16
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29027122/hi1a-as-a-novel-neuroprotective-agent-for-ischemic-stroke-by-inhibition-of-acid-sensing-ion-channel-1a
#17
Yandong Ren, Chengchong Li, Jinlong Chang, Rui Wang, Yuhua Wang, Xiang-Ping Chu
Strokes are the second-leading cause of death worldwide, and the cellular and molecular mechanisms underlying stroke-induced brain damage are still uncertain. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA). However, rtPA has a narrow therapeutic timeframe of 3-4.5 h, and only approximately 5% of stroke patients can benefit from rtPA treatment. Neuroprotective agents, such as N-methyl-D-aspartate receptor antagonists, have shown great promise in preclinical studies...
October 13, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29026538/plasma-and-cerebrospinal-fluid-interleukin-1%C3%AE-during-lipopolysaccharide-induced-systemic-inflammation-in-ewes-implanted-or-not-with-slow-release-melatonin
#18
Janina Skipor, Marta Kowalewska, Aleksandra Szczepkowska, Anna Majewska, Tomasz Misztal, Marek Jalynski, Andrzej P Herman, Katarzyna Zabek
BACKGROUND: Interleukin-1β (IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid (CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29026104/cetsa-quantitatively-verifies-in-vivo-target-engagement-of-novel-ripk1-inhibitors-in-various-biospecimens
#19
Tsuyoshi Ishii, Takuro Okai, Misa Iwatani-Yoshihara, Manabu Mochizuki, Satoko Unno, Masako Kuno, Masato Yoshikawa, Sachio Shibata, Masanori Nakakariya, Takatoshi Yogo, Tomohiro Kawamoto
The proof of target engagement (TE) is a key element for evaluating potential investment in drug development. The cellular thermal shift assay (CETSA) is expected to facilitate direct measurement of intracellular TE at all stages of drug development. However, there have been no reports of applying this technology to comprehensive animal and clinical studies. This report demonstrates that CETSA can not only quantitatively evaluate the drug-TE in mouse peripheral blood, but also confirm TE in animal tissues exemplified by using the receptor interacting protein 1 kinase (RIPK1) lead compound we have developed...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025866/declining-levels-of-functionally-specialized-synaptic-proteins-in-plasma-neuronal-exosomes-with-progression-of-alzheimer-s-disease
#20
Edward J Goetzl, Erin L Abner, Gregory A Jicha, Dimitrios Kapogiannis, Janice B Schwartz
Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN2α), with their respective postsynaptic functional partners, GluA4-containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1), enhance excitatory synaptic activity in some areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in the brain tissues of participants with Alzheimer's disease (AD) correlates with cognitive losses, plasma neuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics...
October 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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