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Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung, Chi-Hao Luan, Frank J Gonzalez, Kalipada Pahan
Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα...
October 17, 2016: Nature Chemical Biology
Mika Nishihara, Genki N Kanda, Tetsuya Suzuki, Shin'ichiro Yamakado, Hideyoshi Harashima, Hiroyuki Kamiya
Histone acetylation is associated with the activation of genes on chromosomes. Transgene expression from plasmid DNA might be increased by the acetylation of histones bound to plasmid DNA. To examine this hypothesis, we employed a positive feedback system, using a fusion protein of the sequence-specific DNA binding domain of yeast GAL4 and the histone acetyltransferase (HAT) domain of mouse CREB-binding protein (GAL4-HAT), in which GAL4-HAT promotes its own expression as well as that of a reporter gene product (luciferase)...
October 13, 2016: Journal of Bioscience and Bioengineering
Hanne Mette Hoffmann, Nadine Crouzin, Estefanía Moreno, Noora Raivio, Silvia Fuentes, Peter J McCormick, Jordi Ortiz, Michel Vignes
BACKGROUND: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors (mGluR1/5), with allosteric modulators showing particular promise. METHODS: We evaluated the capacity of mGluR1/5 receptors to induce functional responses in ex vivo striatal slices from rats with 1) acute cocaine self-administration (CSA), 2) chronic CSA and 3) 60 days CSA withdrawal by westernblot and extracellular recordings of synaptic transmission...
October 15, 2016: International Journal of Neuropsychopharmacology
Lengqiu Guo, Zhuangli Guo, Xiaoqing Luo, Rui Liang, Shui Yang, Haigang Ren, Guanghui Wang, Xuechu Zhen
Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats...
October 12, 2016: Neuroscience Letters
Jisung Kim, Siyoung Lee, Bo-Ryoung Choi, Hee Yang, Youjin Hwang, Jung Han Yoon Park, Frank M LaFerla, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane...
October 13, 2016: Molecular Nutrition & Food Research
Lei Zhang, Lu Huang, Kangrong Lu, Yutong Liu, Genghong Tu, Mengjuan Zhu, Li Ying, Jinlan Zhao, N Liu, Fukun Guo, Lin Zhang, Lu Zhang
Synaptic plasticity plays a critical role in cocaine addiction. The dopamine D1 and D3 receptors differentially regulate the cocaine-induced gene expression, structural remodeling and behavioral response. However, how these two receptors coordinately mediate the ultra-structural changes of synapses after cocaine exposure and whether these changes are behaviorally relevant are still not clear. Here, using quantitative electron microscopy, we show that D1 and D3 receptors have distinct roles in regulating cocaine-induced ultra-structural changes of synapses in the nucleus accumbens and caudoputamen...
October 12, 2016: Addiction Biology
Yan Xu, Jie Chen, Lan Xiao, Hee Kyoung Chung, Yuan Zhang, Joseph C Robinson, Jaladanki N Rao, Jian-Ying Wang
The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1 promoter...
October 12, 2016: American Journal of Physiology. Cell Physiology
Xu Liu, Dongxiao Wang, Runqing Zhao, Xianzhe Dong, Yuan Hu, Ping Liu
As two natural oligosaccharide esters, 3,6'-Disinapoyl sucrose (DISS) and tenuifolisideA (TFSA) are originating from the root of Polygala tenuifolia Willd, a traditional Chinese medicine used in treatment of mental disorders. Previous reports have shown that both of them possess in vitro neuroprotective effects by stimulating different upstream pathways related with cyclic AMP-responsive element-binding protein (CREB). In the present study, we investigated the additive neuroprotective effects of DISS and TFSA on Glu-induced damage of SY5Y cells and purposed the possible underlying mechanism...
2016: Frontiers in Pharmacology
Alan J Simmons, Cherié R Scurrah, Eliot T McKinley, Charles A Herring, Jonathan M Irish, M Kay Washington, Robert J Coffey, Ken S Lau
Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples...
October 11, 2016: Science Signaling
Wenbin Zhong, Guoping Pan, Lin Wang, Shiqian Li, Jingsong Ou, Mengyang Xu, Jiwei Li, Biying Zhu, Xiuye Cao, Hongling Ma, Chaowen Li, Jun Xu, Vesa M Olkkonen, Bart Staels, Daoguang Yan
RATIONALE: Macrophage survival within the arterial wall is a central factor contributing to atherogenesis. Oxysterols, major components of oxidized LDL (ox-LDL), exert cytotoxic effects on macrophages. OBJECTIVE: To determine whether ORP4L, an oxysterol-binding protein, affects macrophage survival and the pathogenesis of atherosclerosis. METHODS AND RESULTS: By hiring cell biological approaches and ORP4L(-/-) mice, we show that ORP4L co-expresses with and forms a complex with G&alphaq/11 and PLCβ3 in macrophages...
October 11, 2016: Circulation Research
Daniel García-Pérez, Szilamer Ferenczi, Krisztina J Kovács, M Luisa Laorden, M Victoria Milanés, Cristina Núñez
Drug-withdrawal aversive memories generate a motivational state leading to compulsive drug taking, with plasticity changes in the basolateral amygdala (BLA) being essential in aversive motivational learning. The conditioned-place aversion (CPA) paradigm allows for measuring the negative affective component of drug withdrawal. First, CPA triggers association between negative affective consequences of withdrawal with context (memory consolidation). Afterwards, when the animals are re-exposed to the paired environment, they avoid it due to the association between the context and aversive memories (memory retrieval)...
September 28, 2016: Psychoneuroendocrinology
T Yu, G Yang, Y Hou, X Tang, C Wu, X-A Wu, L Guo, Q Zhu, H Luo, Y-E Du, S Wen, L Xu, J Yin, G Tu, M Liu
Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs...
October 10, 2016: Oncogene
Guoyang Huang, Jiale Diao, Hongjie Yi, Li Xu, Jiajun Xu, Weigang Xu
Spinal cord injury (SCI) is a debilitating disease, effective prevention measures are in desperate need. Our previous work found that hyperbaric oxygen (HBO) preconditioning significantly protected rats from SCI after stimulated diving, and in vitro study further testified that HBO protected primary cultured rat spinal neurons from oxidative insult and oxygen glucose deprivation injury via heat shock protein (HSP) 32 induction. In this study, underlying molecular mechanisms were further investigated. The results showed that a single exposure to HBO significantly increased intracellular levels of reactive oxygen species (ROS) and nitric oxide (NO) and activated MEK1/2, ERK1/2, p38 MAPK, CREB, Bach1 and Nrf2...
September 24, 2016: Redox Biology
Yen-Chih Chen, Hung-Jhen Chen, Wei-Chin Tseng, Jiun-Min Hsu, Tzu-Ting Huang, Chun-Hao Chen, Chun-Liang Pan
Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures...
October 5, 2016: Developmental Cell
Ting Ting Zhao, Keon Sung Shin, Hyun Jin Park, Kyung Sook Kim, Kung Eun Lee, Yoon Jeong Cho, Myung Koo Lee
This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-D-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses...
October 4, 2016: Neuroscience Letters
Shengzhe S, Yongna Z, Song L, Yan L, Jing Z
AIM: To investigate the role of cAMP response element-binding protein (CREB) in the regulation of odonto/osteogenic differentiation of stem cells from the apical papilla (SCAPs). METHODOLOGY: SCAPs were obtained from human impacted third molars (n=15). Isolated SCAPs were transfected with CREB overexpressing/silenced lentivirus. Transfected cells were stained with alizarin red to investigate mineralized nodule formation. The expression of the mineralization-related genes alkaline phosphatase (ALP), collagen type I (Col I), runt-related transcription factor 2 (RUNX2), osterix (OSX), and osteocalcin (OCN), was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR)...
October 7, 2016: International Endodontic Journal
Yan Du, Li Du, Jie Cao, Christian Hölscher, Yongming Feng, Hongliang Su, Yujin Wang, Ke-Ming Yun
Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from the Chinese herbs Corydalis and Stephania and has been used in many traditional Chinese herbal preparations for its sedative, analgesic and hypnotic properties. Previous studies demonstrated that l-THP has antagonistic activity on dopamine receptors; thus, it may have potential therapeutic effects on drug abuse. However, whether l-THP affects ketamine-induced conditioned place preference (CPP) remains unclear. Therefore, the present study was designed to evaluate the effects of l-THP on the rewarding behavior of ketamine through CPP...
October 3, 2016: Behavioural Brain Research
Mario Rodríguez, Saioa Márquez, Juan Vladimir de la Rosa, Sara Alonso, Antonio Castrillo, Mariano Sánchez Crespo, Nieves Fernández
CREB and STAT3 may control inflammation by several mechanisms, one of the best characterized is the induction of the expression of the anti-inflammatory cytokine IL-10. STAT3 also down-regulates the production of pro-inflammatory cytokines induced by ITAM-coupled receptors, a mechanism termed cross-inhibition. Because signaling via ITAM-dependent mechanisms is a hallmark of fungal pattern receptors, STAT3 activation might be involved in the cross-inhibition associated with invasive fungal infections. The fungal surrogate zymosan produced the phosphorylation of Y705-STAT3 and the expression of Ifnb1 and Socs3, but did not induce the IFN-signature cytokines Cxcl9 and Cxcl10 in BM-derived dendritic cells...
October 6, 2016: Immunology
Kihwan Lee, Hyunju Kim, Kyongman An, Oh-Bin Kwon, Sungjun Park, Jin Hee Cha, Myoung-Hwan Kim, Yoontae Lee, Joung-Hun Kim, Kwangwook Cho, Hye-Sun Kim
MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer's disease (AD). We found that oligomeric Aβ1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p...
October 6, 2016: Scientific Reports
Stefan J Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka Iii, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin R Larsen, Soile Tapio
Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates...
September 30, 2016: Oncotarget
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