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https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#1
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346141/insights-into-electrosensory-organ-development-physiology-and-evolutionfrom-a-lateral-line-enriched-transcriptome
#2
Melinda S Modrell, Mike Lyne, Adrian R Carr, Harold H Zakon, David Buckley, Alexander S Campbell, Marcus C Davis, Gos Micklem, Clare Vh Baker
The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula)...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28345579/inhibition-of-delta-secretase-improves-cognitive-functions-in-mouse-models-of-alzheimer-s-disease
#3
Zhentao Zhang, Obiamaka Obianyo, Elfriede Dall, Yuhong Du, Haian Fu, Xia Liu, Seong Su Kang, Mingke Song, Shan-Ping Yu, Chiara Cabrele, Mario Schubert, Xiaoguang Li, Jian-Zhi Wang, Hans Brandstetter, Keqiang Ye
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344883/acquisition-of-tumor-cell-phenotypic-diversity-along-the-emt-spectrum-under-hypoxic-pressure-consequences-on-susceptibility-to-cell-mediated-cytotoxicity
#4
Stéphane Terry, Stéphanie Buart, Tuan Zea Tan, Gwendoline Gros, Muhammad Zaeem Noman, James B Lorens, Fathia Mami-Chouaib, Jean Paul Thiery, Salem Chouaib
Tumor escape to immunosurveillance and resistance to immune attacks present a major hurdle in cancer therapy, especially in the current era of new cancer immunotherapies. We report here that hypoxia, a hallmark of most solid tumors, orchestrates carcinoma cell heterogeneity through the induction of phenotypic diversity and the acquisition of distinct epithelial-mesenchymal transition (EMT) states. Using lung adenocarcinoma cells derived from a non-metastatic patient, we demonstrated that hypoxic stress induced phenotypic diversity along the EMT spectrum, with induction of EMT transcription factors (EMT-TFs) SNAI1, SNAI2, TWIST1, and ZEB2 in a hypoxia-inducible factor-1α (HIF1A)-dependent or -independent manner...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344592/dysbindin-deficiency-modifies-the-expression-of-gaba-neuron-and-ion-permeation-transcripts-in-the-developing-hippocampus
#5
Jennifer Larimore, Stephanie A Zlatic, Miranda Arnold, Kaela S Singleton, Rebecca Cross, Hannah Rudolph, Martha V Bruegge, Andrea Sweetman, Cecilia Garza, Eli Whisnant, Victor Faundez
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28344334/the-kif1a-homolog-unc-104-is-important-for-spontaneous-release-postsynaptic-density-maturation-and-perisynaptic-scaffold-organization
#6
Yao V Zhang, Shabab B Hannan, Jeannine V Kern, Doychin T Stanchev, Baran Koç, Thomas R Jahn, Tobias M Rasse
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104(bris), impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343869/spatiotemporal-regulation-of-synaptic-vesicle-fusion-sites-in-central-synapses
#7
Dario Maschi, Vitaly A Klyachko
The number and availability of vesicle release sites at the synaptic active zone (AZ) are critical factors governing neurotransmitter release; yet, these fundamental synaptic parameters have remained undetermined. Moreover, how neural activity regulates the spatiotemporal properties of the release sites within individual central synapses is unknown. Here, we combined a nanoscale imaging approach with advanced image analysis to detect individual vesicle fusion events with ∼27 nm localization precision at single hippocampal synapses under physiological conditions...
March 18, 2017: Neuron
https://www.readbyqxmd.com/read/28343802/-the-effect-of-methylphenidate-on-appetite-and-weight
#8
R Bou Khalil, N Fares, Y Saliba, J Tamraz, S Richa
OBJECTIVES: To better delineate in the medical literature the effect of methylphenidate on weight and appetite. METHODS: A search on PubMed was carried out for articles published with no restrictions on language or year of publication using the terms: "methylphenidate"; "weight"; "appetite". RESULTS: Methylphenidate increases dopamine and noradrenaline in synapses because of its blockage of the transporters of these monoamines in the frontal cortex and insular lobe...
March 23, 2017: L'Encéphale
https://www.readbyqxmd.com/read/28343438/hsa-mir-27b-is-up-regulated-in-cytomegalovirus-infected-human-glioma-cells-targets-engrailed-2-and-inhibits-its-expression
#9
Linqian Wang, Ming Yang, Shijing Liao, Wei Liu, Gan Dai, Guojun Wu, Liyu Chen
Human cytomegalovirus (HCMV) dormant infection can alter the expression of the hosts' microRNAs (miRNAs) and impact on the regulation of target genes. To investigate the differentially expressed miRNAs induced by HCMV in human glioma U251 cells, a comprehensive miRNA screen was performed. As a result, 19 up-regulated and 14 down-regulated miRNAs were determined. Of these, hsa-miR-27b (miR-27b) attracted our attention. MiR-27b levels in U251 cells increased 7.70-fold, 8.64-fold, and 4.78-fold, respectively, post 24 h, 48 h, and 72 h HCMV infection, compared to those in the mimic-infected cells, and this up-regulation was further confirmed by quantitative RT-PCR...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28343411/3d-liver-surgery-simulation-computer-assisted-surgical-planning-with-3d-simulation-software-and-3d-printing
#10
Yukio Oshiro, Nobuhiro Ohkohchi
To perform accurate hepatectomy without injury, it is necessary to understand the anatomical relationship among the branches of Glisson's sheath, hepatic veins, and tumor. In Japan, three-dimensional (3D) preoperative simulation for liver surgery is becoming increasingly common, and liver 3D modeling and 3D hepatectomy simulation by 3D analysis software for liver surgery have been covered by universal healthcare insurance since 2012. Herein, we review the history of virtual hepatectomy using computer-aided surgery (CAS) and our research to date, and we discuss the future prospects of CAS...
March 27, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28342263/surgical-pitfalls-of-jejunal-vein-anatomy-in-pancreaticoduodenectomy
#11
Yoshiya Ishikawa, Daisuke Ban, Satoshi Matsumura, Yusuke Mitsunori, Takanori Ochiai, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe
BACKGROUND: Pancreaticoduodenectomy (PD) is the standard surgical procedure for treating pancreatic head cancers. Considerable knowledge of proximal jejunal and pancreatic vein anatomy is a prerequisite for performing PD surgery safely, yet there appear to be no detailed descriptions of first and second jejunal vein (J1V, J2V) anatomy available in the literature. STUDY DESIGN: Adults with hepatobiliary-pancreatic disease underwent multidetector-row computed tomography with intravenous contrast (n=155), and SYNAPSE 3D(®) (Fujifilm Medical, Tokyo, Japan) was used to generate 3D-CT images...
March 24, 2017: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28341478/importance-of-major-histocompatibility-complex-of-class-i-mhc-i-expression-for-astroglial-reactivity-and-stability-of-neural-circuits-in-vitro
#12
André Luis Bombeiro, Rafaela Chitarra Rodrigues Hell, Gustavo Ferreira Simões, Mateus Vidigal de Castro, Alexandre Leite Rodrigues de Oliveira
MHC-I molecules are involved in the antigenic presentation of cytosol-derived peptides to CD8T lymphocytes. In the nervous system, MHC-I expression is low to absent, occurring only during certain phases of development and aging or after injuries. The involvement of MHC-I in synaptic plasticity has been reported and, following lesion, astrocytes become reactive, limiting tissue damage. Such cells also attempt to restore homeostasis by secreting cytokines and neurotrophic factors. Moreover, astrocytes modulate synapse function, by taking up and releasing neurotransmitters and by limiting the synaptic cleft...
March 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28341461/sequential-therapy-of-anti-nogo-a-antibody-treatment-and-treadmill-training-leads-to-cumulative-improvements-after-spinal-cord-injury-in-rats
#13
Kinon Chen, Barnaby C Marsh, Matthew Cowan, Yazi D Al'Joboori, Sylvain Gigout, Calvin C Smith, Neil Messenger, Nikita Gamper, Martin E Schwab, Ronaldo M Ichiyama
Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2weeks) and then either left untrained or step-trained starting 3weeks after injury for 8weeks...
March 21, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28338525/orexin-action-on-oxytocin-neurons-in-the-paraventricular-nucleus-of-the-hypothalamus
#14
Yuko Maejima, Shinichi Takahashi, Katsuya Takasu, Seiichi Takenoshita, Yoichi Ueta, Kenju Shimomura
Oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus play an important role in food intake regulation. It has been shown that the secretion of oxytocin from the hypothalamus shows a diurnal circadian rhythmic pattern and disturbance of this pattern leads to the development of obesity. However, whether oxytocin secretion from the PVN has a diurnal pattern remains unknown. Here, we show that oxytocin secretion from the PVN does have a diurnal pattern and that the terminals of orexin neurons, the neuropeptide responsible for regulating the sleep-wake rhythm, are synapsed with PVN oxytocin neurons...
March 23, 2017: Neuroreport
https://www.readbyqxmd.com/read/28337539/homer1-vesl-1-in-the-rat-esophagus-focus-on-myenteric-plexus-and-neuromuscular-junction
#15
J Zimmermann, W L Neuhuber, M Raab
Homer1, a scaffolding protein of the postsynaptic density (PSD), enriched at excitatory synapses is known to anchor and modulate group I metabotropic glutamate receptors (mGluRs) and different channel- and receptor-proteins. Homer proteins are expressed in neurons of different brain regions, but also in non-neuronal tissues like skeletal muscle. Occurrence and location of Homer1 and mGluR5 in myenteric plexus and neuromuscular junctions (NMJ) of rat esophagus have yet not been characterized. We located Homer1 and mGluR5 immunoreactivity (-iry) in rat esophagus and focused on myenteric neurons, intraganglionic laminar endings (IGLEs) and NMJs, using double- and triple-label immunohistochemistry and confocal laser scanning microscopy...
March 23, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#16
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337128/connexin36-expression-in-the-mammalian-retina-a-multiple-species-comparison
#17
Tamás Kovács-Öller, Gábor Debertin, Márton Balogh, Alma Ganczer, József Orbán, Miklós Nyitrai, Lajos Balogh, Orsolya Kántor, Béla Völgyi
Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans. However, a comparison of Cx36 GJ distribution in retinas of humans and popular animal models has not been presented. To this end a multiple-species comparison was performed in retinas of 12 mammals including humans to survey the Cx36 distribution...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28336773/elks1-helps-neuronal-synapses-diversify
#18
Ben Short
Study reveals how neurons vary the properties of individual synapses by recruiting different Munc13 proteins to presynaptic active zones.
March 23, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28336441/chronic-stress-induced-dendritic-reorganization-and-abundance-of-synaptosomal-pka-dependent-cp-ampa-receptor-in-the-basolateral-amygdala-in-a-mouse-model-of-depression
#19
Eun-Surk Yi, Seikwan Oh, Jang-Kyu Lee, Yea-Hyun Leem
Chronic stress is a precipitating factor for disorders including depression. The basolateral amygdala (BLA) is a critical substrate that interconnects with stress-modulated neural networks to generate emotion- and mood-related behaviors. The current study shows that 3 h per day of restraint stress for 14 days caused mice to exhibit long-term depressive behaviors, manifested by disrupted sociality and despair levels, which were rescued by fluoxetine. These behavioral changes corresponded with morphological and molecular changes in BLA neurons, including chronic stress-elicited increases in arborization, dendritic length, and spine density of BLA principal neurons...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28335015/the-synaptic-function-of-parkin
#20
Jenny Sassone, GiuliaMaia Serratto, Flavia Valtorta, Vincenzo Silani, Maria Passafaro, Andrea Ciammola
Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time...
February 23, 2017: Brain: a Journal of Neurology
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