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https://www.readbyqxmd.com/read/28109039/nkx2-5-regulates-endothelin-converting-enzyme-1-during-pharyngeal-arch-patterning
#1
Jennifer M Iklé, Andre L P Tavares, Marisol King, Hailei Ding, Sophie Colombo, Beth A Firulli, Anthony B Fiulli, Kimara L Targoff, Deborah Yelon, David E Clouthier
In gnathostomes, dorsoventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediates this process is Endothelin-1 (EDN1). Loss of EDN1 binding to the Endothelin-A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate-limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme-1 (ECE1)...
January 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28108498/mglur2-versus-mglur3-metabotropic-glutamate-receptors-in-primate-dorsolateral-prefrontal-cortex-postsynaptic-mglur3-strengthen-working-memory-networks
#2
Lu E Jin, Min Wang, Veronica C Galvin, Taber C Lightbourne, Peter Jeffrey Conn, Amy F T Arnsten, Constantinos D Paspalas
The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K(+) channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission...
January 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28108422/role-of-microglia-autophagy-in-microglia-activation-after-traumatic-brain-injury
#3
Yichao Jin, Ran Wang, Shaofeng Yang, Xiaohua Zhang, Jiong Dai
OBJECTIVE: Role of microglia autophagy in microglia activation after traumatic brain injury (TBI) remains elusive. Here, we evaluated role of microglia autophagy in microglia activation after traumatic brain injury (TBI) in rats. METHODS: TBI was induced by a fluid percussion TBI device. All rats were killed at 24 h after TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; Immunohistochemistry and western blotting of IBA-1 was used to determine the changes of microglia activation; Double staining of microtubule-associated protein light chain 3 (LC-3), Beclin-1 and IBA-1 was used to assess the changes of microglia autophagy; enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor receptor-alpha (TNF-α) and interleukin-1β (IL-1β) was used to evaluate the changes of inflammatory responses; terminal deoxynucleoitidyl transferase mediated nick end labeling staining (TUNEL) was used to determine cell death in ipsilateral hippocampus...
January 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28107913/quantitative-structure-retention-relationship-model-for-the-determination-of-naratriptan-hydrochloride-and-its-impurities-based-on-artificial-neural-networks-coupled-with-genetic-algorithm
#4
Mikołaj Mizera, Anna Krause, Przemysław Zalewski, Robert Skibiński, Judyta Cielecka-Piontek
Mathematical modeling of Quantitative Structure - Property Relationships met great interest in fields of in silico drug design and more recently, pharmaceutical analysis. In our approach we proposed automated method of creation Quantitative Structure-Retention Relationship (QSRR) for analysis of triptans, selective serotonin 5-HT1 receptor agonists used for the treatment of acute headache. The method was created using hybrid machine learning approach, namely Genetic algorithm (GA) coupled with artificial neutral networks (ANN)...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28106040/the-effects-of-prior-stress-on-anxiety-like-responding-to-intra-bnst-pituitary-adenylate-cyclase-activating-polypeptide-pacap-in-male-and-female-rats
#5
S Bradley King, Kim R Lezak, Micaela O'Reilly, Donna J Toufexis, William A Falls, Karen Braas, Victor May, Sayamwong E Hammack
Chronic or repeated exposure to stressful stimuli can result in several maladaptive consequences, including increased anxiety-like behaviors and altered peptide expression in anxiety-related brain structures. Among these structures, the bed nucleus of the stria terminalis (BNST) has been implicated in emotional behaviors as well as regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. In male rodents, chronic variate stress (CVS) has been shown to increase BNST pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate PAC1 receptor transcript, and BNST PACAP signaling may mediate the maladaptive changes associated with chronic stress...
January 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28105773/exosomal-biomarkers-of-brain-insulin-resistance-associated-with-regional-atrophy-in-alzheimer-s-disease
#6
Roger J Mullins, Maja Mustapic, Edward J Goetzl, Dimitrios Kapogiannis
: Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. CONTROLS: Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ42 )...
January 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#7
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#8
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28100828/an-integrated-modelling-framework-for-neural-circuits-with-multiple-neuromodulators
#9
Alok Joshi, Vahab Youssofzadeh, Vinith Vemana, T M McGinnity, Girijesh Prasad, KongFatt Wong-Lin
Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28098409/trpv4-contributes-to-resting-membrane-potential-in-retinal-m%C3%A3-ller-cells-implications-in-cell-volume-regulation
#10
Vanina Netti, Juan Fernández, Maia Kalstein, Alejandro Pizzoni, Gisela Di Giusto, Valeria Rivarola, Paula Ford, Claudia Capurro
Neural activity alters osmotic gradients favoring cell swelling in retinal Müller cells. This swelling is followed by a regulatory volume decrease (RVD), partially mediated by an efflux of KCl and water. The transient receptor potential channel 4 (TRPV4), a nonselective calcium channel, has been proposed as a candidate for mediating intracellular Ca(2+) elevation induced by swelling. We previously demonstrated in a human Müller cell line (MIO-M1) that RVD strongly depends on ion channel activation and, consequently, on membrane potential (Vm )...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28098344/inhibition-of-oxytocin-and-vasopressin-neuron-activity-in-rat-hypothalamic-paraventricular-nucleus-by-relaxin-3-rxfp3-signalling
#11
Alan Kania, Anna Czerw, Agnieszka Grabowiecka, Camila de Ávila, Tomasz Blasiak, Zenon Rajfur, Marian H Lewandowski, Grzegorz Hess, Elena Timofeeva, Andrew L Gundlach, Anna Blasiak
KEY-POINTS: Relaxin-3 is a stress-responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated a direct, RXFP3-dependent, inhibitory action of relaxin-3 on oxytocin and vasopressin PVN neuron electrical activity, a putative cellular mechanism of orexinergic actions of relaxin-3. We observed a Gαi/o -protein-dependent inhibitory influence of selective RXFP3 activation on PVN neuronal activity in vitro and demonstrated a direct action of RXFP3 activation on oxytocin and vasopressin PVN neurons, confirmed by their abundant expression of RXFP3 mRNA...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28093190/ghrelin-fibers-from-lateral-hypothalamus-project-to-nucleus-tractus-solitaries-and-are-involved-in-gastric-motility-regulation-in-cisplatin-treated-rats
#12
Yanling Gong, Yang Liu, Fei Liu, Shasha Wang, Hong Jin, Feifei Guo, Luo Xu
Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS)...
January 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#13
REVIEW
Grzegorz Dobrzanski, Małgorzata Kossut
The DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technique is a new chemogenetic approach allowing for selective and remote control of neural activity with a high degree of spatial resolution. Since its discovery in 2007 the DREADD technique was successfully employed into basic research, and together with the optogenetic method provided so far the best tool to influence the activity of the brain circuits and cell populations. The first aim of this review was to concisely describe the technique with regard to such issues like the history of its development, biochemistry as well as modes of the designer receptors delivery and expression...
October 29, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28092438/biofunctionalization-of-nerve-interface-via-biocompatible-polymer-roughened-pt-black-on-cuff-electrode-for-chronic-recording
#14
Yi Jae Lee, Han-Jun Kim, Ji Yoon Kang, Sun Hee Do, Soo Hyun Lee
Peripheral nerve cuff electrodes with roughened Pt black (BPt) are coated with polyethylene glycol (PEG) and Nafion (NF). Although the influence of coated PEG and Nafion on roughened BPt on the electrical properties is weak, the cuff electrode with BPt/PEG and BPt/Nafion exhibits some very important properties. For example, it markedly decreases interfacial impedance, increases charge storage capacity (CSC) due to retaining the BPt surface structure, good stability without exfoliation in repetitive cyclic voltammetry scanning because it is protected by PEG or Nafion coating...
January 16, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28089918/cardiovascular-and-respiratory-activity-of-pk20-opioid-and-neurotensin-hybrid-peptide-in-anesthetized-and-awake-rats
#15
Katarzyna Kaczyńska, Piotr Wojciechowski, Monika Jampolska, Andrzej W Lipkowski, Patrycja Kleczkowska
AIM: Chimeric compound - PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats. METHODS: The effects of PK20 (1mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28089705/so-as-we-worry-we-weigh-visible-burrow-system-stress-and-visceral-adiposity
#16
REVIEW
Michelle T Foster
The visible borrow system (VBS) simulates a natural rodent habitat that supports genuine stress provoking social interactions. This model allows investigation of behavioral, neural and endocrine alterations caused by chronic stress. The Sakai lab further used this model to investigate metabolic outcomes of stress in relation to dominance hierarchies formed within the VBS. Communal social conflict occurs among all VBS rats, but only the SUB rats succumb to the redistribution of lipids in the visceral cavity and consequent metabolic dysregulation, such as hyper-insulinemia...
January 12, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#17
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28088536/targeting-sonic-hedgehog-signaling-in-neurological-disorders
#18
REVIEW
Sita Sharan Patel, Sunil Tomar, Diksha Sharma, Neeraj Mahindroo, Malairaman Udayabanu
Sonic hedgehog (Shh) signaling influences neurogenesis and neural patterning during the development of central nervous system. Dysregulation of Shh signaling in brain leads to neurological disorders like autism spectrum disorder, depression, dementia, stroke, Parkinson's diseases, Huntington's disease, locomotor deficit, epilepsy, demyelinating disease, neuropathies as well as brain tumors. The synthesis, processing and transport of Shh ligand as well as the localization of its receptors and signal transduction in the central nervous system has been carefully reviewed...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#19
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28081529/zika-virus-induced-microcephaly-and-its-possible-molecular-mechanism
#20
Md Imam Faizan, Mohd Abdullah, Sher Ali, Irshad H Naqvi, Anwar Ahmed, Shama Parveen
Zika virus is an arthropod-borne re-emerging pathogen associated with the global pandemic of 2015-2016. The devastating effect of Zika viral infection is reflected by its neurological manifestations such as microcephaly in newborns. This scenario evoked our interest to uncover the neurotropic localization, multiplication of the virus, and the mechanism of microcephaly. The present report provides an overview of a possible molecular mechanism of Zika virus-induced microcephaly based on recent publications. Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells...
January 13, 2017: Intervirology
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