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https://www.readbyqxmd.com/read/28811543/4-e-p-tolylimino-methylbenzene-1-2-diol-timbd-suppresses-hiv1-gp120-mediated-production-of-il6-and-il8-but-not-ccl5
#1
Fatma Abdalla, Anantha Nookala, Subhash B Padhye, Anil Kumar, Hari K Bhat
Human immunodeficiency virus (HIV) has been associated with inflammatory effects that may potentially result in neurodegenerative changes and a number of newer chemotherapeutic agents are being tested to ameliorate these effects. In this study, we investigated the anti-neuroinflammatory activity of a novel resveratrol analog 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) against HIV1-gp120 induced neuroinflammation in SVG astrocytes. SVG astrocytic cells were pretreated with TIMBD or resveratrol (RES) and then transfected with a plasmid encoding HIV1-gp120...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802560/traumatic-brain-injuries-during-development-disrupt-dopaminergic-signaling
#2
Kate Karelina, Kristopher R Gaier, Zachary M Weil
Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI on dopaminergic dysfunction and its relationship with substance abuse have not been investigated. In order to determine the effect of juvenile brain injury on dopaminergic signaling, female mice were injured at 21days of age and then beginning seven weeks later were assessed for behavioral sensitization to amphetamine, a drug that increases synaptic dopamine availability...
August 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28762073/alterations-in-brain-activation-in-response-to-prolonged-morphine-withdrawal-induced-behavioral-inflexibility-in-rats
#3
Chengji Piao, Tiane Liu, Lian Ma, Xuekun Ding, Xingyue Wang, Xing Chen, Ying Duan, Nan Sui, Jing Liang
RATIONALE: The inability to stop a repetitive maladaptive behavior is a main problem in addictive disorders. Neuroadaptations that are associated with behavioral inflexibility may be involved in compulsive drug use. OBJECTIVES: The aim of the present study was to investigate the pattern of behavioral inflexibility during morphine withdrawal and map brain activation that is linked to alterations in flexibility. METHODS: We first analyzed the effects of chronic morphine exposure on reversal learning after 2-week (short-term) and 6-week (prolonged) morphine withdrawal...
July 31, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28745316/elevation-of-adenylate-energy-charge-by-angiopoietin-like-4-enhances-epithelial-mesenchymal-transition-by-inducing-14-3-3%C3%AE-expression
#4
Z Teo, M K Sng, J S K Chan, M M K Lim, Y Li, L Li, T Phua, J Y H Lee, Z W Tan, P Zhu, N S Tan
Metastatic cancer cells acquire energy-intensive processes including increased invasiveness and chemoresistance. However, how the energy demand is met and the molecular drivers that coordinate an increase in cellular metabolic activity to drive epithelial-mesenchymal transition (EMT), the first step of metastasis, remain unclear. Using different in vitro and in vivo EMT models with clinical patient's samples, we showed that EMT is an energy-demanding process fueled by glucose metabolism-derived adenosine triphosphate (ATP)...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28712684/cerebellar-perineuronal-nets-in-cocaine-induced-pavlovian-memory-site-matters
#5
Maria Carbo-Gas, Josep Moreno-Rius, Julian Guarque-Chabrera, Dolores Vazquez-Sanroman, Isis Gil-Miravet, Daniela Carulli, Freek Hoebeek, Chris De Zeeuw, Carla Sanchis-Segura, Marta Miquel
One of the key mechanisms for the stabilization of synaptic changes near the end of critical periods for experience-dependent plasticity is the formation of specific lattice extracellular matrix structures called perineuronal nets (PNNs). The formation of drug memories depends on local circuits in the cerebellum, but it is unclear to what extent it may also relate to changes in their PNN. Here, we investigated changes in the PNNs of the cerebellum following cocaine-induced preference conditioning. The formation of cocaine-related preference memories increased expression of PNN-related proteins surrounding Golgi inhibitory interneurons as well as that of cFos in granule cells at the apex of the cerebellar cortex...
July 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28636317/downsizing-proto-oncogene-cfos-to-short-helix-constrained-peptides-that-bind-jun
#6
Daniel Baxter, Samuel R Perry, Timothy A Hill, W Mei Kok, Nathan R Zaccai, R Leo Brady, David P Fairlie, Jody M Mason
The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of Fos and Jun protein subunits, their leucine-rich helical sequences entwining into a coiled-coil structure. This study reports on downsizing the proto-oncogene cFos protein (380 residues) to shorter peptides (37-25 residues) modified with helix-inducing constraints to enhance binding to Jun. A crystal structure is reported for a 37-residue Fos-derived peptide (FosW) bound to Jun. This guided iterative downsizing of FosW to shorter peptide sequences that were constrained into stable water-soluble α-helices by connecting amino acid side chains to form cyclic pentapeptide components...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28602745/systemic-estradiol-administration-to-ovariectomized-rats-facilitates-thermoregulatory-behavior-in-a-cold-environment
#7
Yuki Uchida, Kei Nagashima, Kazunari Yuri
Rats place their tails underneath their bodies in the cold (tail-hiding behavior), which is a behavioral indicator of thermoregulation. The aim of the present study was to elucidate the effect of estradiol (E2) on tail-hiding behavior and neural activity assessed by immunohistochemistry. Ovariectomized rats were implanted with a silastic tube with or without E2 underneath the dorsal skin (E2(-) and E2(+) groups), and exposed to 27°C, 16°C, and 10°C for 2h with continuous body temperature (Tb), tail skin temperature (Ttail), and behavioral measurements...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28583411/increased-temporal-discounting-after-chronic-stress-in-chl1-deficient-mice-is-reversed-by-5-ht2c-agonist-ro-60-0175
#8
Mona Buhusi, Kaitlin Olsen, Catalin V Buhusi
Schizophrenia is a neurodevelopmental disorder in which impaired decision-making and goal-directed behaviors are core features. One of the genes associated with schizophrenia is the Close Homolog of L1 (CHL1); CHL1-deficient mice are considered a model of schizophrenia-like deficits, including sensorimotor gating, interval timing and spatial memory impairments. Here we investigated temporal discounting in CHL1-deficient (KO) mice and their wild-type littermates. Although no discounting differences were found under baseline conditions, CHL1-KO mice showed increased impulsive choice following chronic unpredictable stress (fewer % larger-later choices, and reduced area under the discounting curve)...
August 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28579251/perinatal-exposure-to-organohalogen-pollutants-decreases-vasopressin-content-and-its-mrna-expression-in-magnocellular-neuroendocrine-cells-activated-by-osmotic-stress-in-adult-rats
#9
Samuel Mucio-Ramírez, Eduardo Sánchez-Islas, Edith Sánchez-Jaramillo, Margarita Currás-Collazo, Victor R Juárez-González, Mhar Y Álvarez-González, L E Orser, Borin Hou, Francisco Pellicer, Prasada Rao S Kodavanti, Martha León-Olea
Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported that rats perinatally exposed to Aroclor-1254 (A1254) and DE-71 (commercial mixtures of PCBs and PBDEs) decrease somatodendritic vasopressin (AVP) release while increasing plasma AVP responses to osmotic activation, potentially emptying AVP reserves required for body-water balance...
August 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28552607/cfos-sox9-axis-reprograms-bone-marrow-derived-mesenchymal-stem-cells-into-chondroblastic-osteosarcoma
#10
Yunlong He, Wentao Zhu, Min Hwa Shin, Joy Gary, Chengyu Liu, Wendy Dubois, Shelley B Hoover, Shunlin Jiang, Eryney Marrogi, Beverly Mock, R Mark Simpson, Jing Huang
Bone marrow-derived mesenchymal stem cells (BMSCs) are proposed as the cells of origin of several subtypes of osteosarcoma (OS). However, signals that direct BMSCs to form different subtypes of OS are unclear. Here we show that the default tumor type from spontaneously transformed p53 knockout (p53_KO) BMSCs is osteoblastic OS. The development of this default tumor type caused by p53 loss can be overridden by various oncogenic signals: RAS reprograms p53_KO BMSCs into undifferentiated sarcoma, AKT enhances osteoblastic OS, while cFOS promotes chondroblastic OS formation...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-protumorigenic-actions-via-neutrophil-elastase
#11
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here, it is reported that granulocytic myeloid-derived suppressor cells (MDSC) are the predominant tumor-infiltrating cells in prostate cancer xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28267150/ablation-of-neuropsin-neuregulin-1-signaling-imbalances-erbb4-inhibitory-networks-and-disrupts-hippocampal-gamma-oscillation
#12
M Kawata, S Morikawa, S Shiosaka, H Tamura
Parvalbumin-expressing interneurons are pivotal for the processing of information in healthy brain, whereas the coordination of these functions is seriously disrupted in diseased brain. How these interneurons in the hippocampus participate in pathological functions remains unclear. We previously reported that neuregulin 1 (NRG1)-ErbB4 signaling, which is actuated by neuropsin, is important for coordinating brain plasticity. Neuropsin cleaves mature NRG1 (bound to extracellular glycosaminoglycans) in response to long-term potentiation or depression, liberating a soluble ligand that activates its receptor, ErbB4...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28265687/activation-of-the-thalamic-parafascicular-nucleus-by-electrical-stimulation-of-the-peripheral-vestibular-nerve-in-rats
#13
Nari Kim, Myoung Ae Choi, Ho Koo, Byung Rim Park, Sang Who Han, Chaejoon Cheong, Min Sun Kim
The parafascicular nucleus (PFN) of the thalamus is a primary structure in the feedback circuit of the basal ganglia-thalamo-cortical system, as well as in the neural circuit of the vestibulo-thalamo-striatal pathway. We investigated the characteristics of the functional connectivity between the peripheral vestibular system and the PFN in rats. A single electrical stimulation was applied to the horizontal semicircular canal nerve in the peripheral vestibular end-organs. This resulted in polysynaptic local field potentials (LFPs) in the PFN, which were composed of long-lasting multiple waves...
May 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28111074/apoe2-apoe3-and-apoe4-differentially-stimulate-app-transcription-and-a%C3%AE-secretion
#14
Yu-Wen Alvin Huang, Bo Zhou, Marius Wernig, Thomas C Südhof
Human apolipoprotein E (ApoE) apolipoprotein is primarily expressed in three isoforms (ApoE2, ApoE3, and ApoE4) that differ only by two residues. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), ApoE3 is neutral, and ApoE2 is protective. How ApoE isoforms influence AD pathogenesis, however, remains unclear. Using ES-cell-derived human neurons, we show that ApoE secreted by glia stimulates neuronal Aβ production with an ApoE4 > ApoE3 > ApoE2 potency rank order. We demonstrate that ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28104309/heightened-cortical-excitability-in-aged-rodents-with-memory-impairment
#15
Rebecca P Haberman, Ming Teng Koh, Michela Gallagher
Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices...
June 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28089665/dissociation-of-morphine-analgesic-effects-in-the-sensory-and-affective-components-of-formalin-induced-spontaneous-pain-in-male-and-female-rats
#16
Lisa R Harton, Janell R Richardson, Alexander Armendariz, Arbi Nazarian
Sex differences in the analgesic effects of morphine have been previously reported in various models that represent the sensory component of pain. However, pain sensation is a complex process that consists of both sensory and affective components. It is presently unclear whether the analgesic effects of morphine between the sensory and affective components of pain are sexually dimorphic. Moreover, differences in morphine dose-response in the two components of pain have not been examined in male and female rats...
March 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28079752/changes-in-dorsal-root-ganglion-gene-expression-in-response-to-spinal-cord-stimulation
#17
Dana M Tilley, David L Cedeño, Courtney A Kelley, Margaret DeMaegd, Ramsin Benyamin, Ricardo Vallejo
BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. METHODS: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours)...
March 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28060340/reprogramming-mouse-embryonic-fibroblasts-with-transcription-factors-to-induce-a-hemogenic-program
#18
Michael G Daniel, Carlos-Filipe Pereira, Jeffrey M Bernitz, Ihor R Lemischka, Kateri Moore
This protocol details the induction of a hemogenic program in mouse embryonic fibroblasts (MEFs) via overexpression of transcription factors (TFs). We first designed a reporter screen using MEFs from human CD34-tTA/TetO-H2BGFP (34/H2BGFP) double transgenic mice. CD34(+) cells from these mice label H2B histones with GFP, and cease labeling upon addition of doxycycline (DOX). MEFS were transduced with candidate TFs and then observed for the emergence of GFP(+) cells that would indicate the acquisition of a hematopoietic or endothelial cell fate...
December 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28053227/a-hypothalamic-circuit-that-controls-body-temperature
#19
Zheng-Dong Zhao, Wen Z Yang, Cuicui Gao, Xin Fu, Wen Zhang, Qian Zhou, Wanpeng Chen, Xinyan Ni, Jun-Kai Lin, Juan Yang, Xiao-Hong Xu, Wei L Shen
The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD)...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28043916/ketamine-accelerates-fear-extinction-via-mtorc1-signaling
#20
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
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