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https://www.readbyqxmd.com/read/28731156/protein-interacting-with-c%C3%A2-kinase-1-modulates-exocytosis-and-katp-conductance-in-pancreatic-%C3%AE-cells
#1
Yunhong Li, Fan Li, Bin Bai, Zhenyong Wu, Xiaolin Hou, Ying Shen, Yin Wang
It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730825/the-implication-of-ampa-receptor-in-synaptic-plasticity-impairment-and-intellectual-disability-in-fragile-x-syndrome
#2
G-R Cheng, X-Y Li, Y-D Xiang, D Liu, S M McClintock, Y Zeng
Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28729845/negative-affect-and-excessive-alcohol-intake-incubate-during-protracted-withdrawal-from-binge-drinking-in-adolescent-but-not-adult-mice
#3
Kaziya M Lee, Michal A Coehlo, Noah R Solton, Karen K Szumlinski
Binge-drinking is common in underage alcohol users, yet we know little regarding the biopsychological impact of binge-drinking during early periods of development. Prior work indicated that adolescent male C57BL6/J mice with a 2-week history of binge-drinking (PND28-41) are resilient to the anxiogenic effects of early alcohol withdrawal. Herein, we employed a comparable Drinking-in-the-Dark model to determine how a prior history of binge-drinking during adolescence (EtOH(adolescents)) influences emotionality (assayed with the light-dark box, marble burying test, and the forced swim test) and the propensity to consume alcohol in later life, compared to animals without prior drinking experience...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28729220/cognitive-enhancement-and-antipsychotic-like-activity-following-repeated-dosing-with-the-selective-m4-pam-vu0467154
#4
Robert W Gould, Michael D Grannan, Barak W Gunter, Jacob Ball, Michael Bubser, Thomas M Bridges, Jurgen Wess, Michael W Wood, Nicholas J Brandon, Mark E Duggan, Colleen M Niswender, Craig W Lindsley, P Jeffrey Conn, Carrie K Jones
Although selective activation of the M1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms...
July 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28728911/effects-of-riluzole-on-spinal-seizure-like-activity-in-the-brainstem-spinal-cord-preparation-of-newborn-rat
#5
Shih Tien Lin, Masayuki Ohbayashi, Toshinori Yamamoto, Hiroshi Onimaru, Mari Kogo
Riluzole blocks persistent Na(+) current, inhibits generation of neuronal bursts and decreases glutamate-induced excitotoxicity. In previous studies of respiratory activity, riluzole suppressed inspiratory-related burst generation activity in rat slice or en bloc preparations. We examined riluzole's effects on inspiratory burst generation and drug-induced seizure-like activity in newborn rat en bloc preparations. Medulla-spinal cord preparations from postnatal day 0-3 Wistar rats were isolated under deep isoflurane anesthesia and were superfused with artificial cerebrospinal fluid equilibrated with 95% O2 and 5% CO2, pH 7...
July 17, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28727040/genome-wide-association-studies-and-meta-analysis-reveal-novel-quantitative-trait-loci-and-pleiotropic-loci-for-swine-head-related-traits
#6
H Chen, T Huang, Z Zhang, B Yang, C Jiang, J Wu, Z Zhou, H Zheng, W Xin, M Huang, M Zhang, C Chen, J Ren, H Ai, L Huang
The pig is an important domestic animal that provides a larger amount of meat and serves as a biomedical animal model for human. Head and facial features are closely linked to identity recognition in mammal communication. To uncover the genetic architecture of swine head and facial features, we constructed 5 experimental pig populations and accurately measured 10 traits related to head and facial features, for which genome-wide association studies and meta-analysis were later carried out. As a result, we identified a total of 24 loci harboring 437 SNP on 8 swine chromosomes (SSC) that surpassed suggestively significant levels, of which 17 loci on 6 chromosomes exceeded the 5% genome-wide significance thresholds...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726541/characterization-of-postsynaptic-calcium-signals-in-the-pyramidal-neurons-of-anterior-cingulate-cortex
#7
Xu-Hui Li, Qian Song, Tao Chen, Min Zhuo
Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28726540/mechanisms-of-the-analgesic-effect-of-calcitonin-on-chronic-pain-by-alteration-of-receptor-or-channel-expression
#8
Akitoshi Ito, Megumu Yoshimura
The polypeptide hormone calcitonin is well known clinically for its ability to relieve osteoporotic back pain and neuropathic pain such as spinal canal stenosis, diabetic neuropathy, chemotherapy-induced neuropathy, and complex regional pain syndrome. Because the analgesic effects of calcitonin have a broad range, the underlying mechanisms of pain relief by calcitonin are largely unknown. However, recent studies using several types of chronic pain models combined with various methods have been gradually clarifying the mechanism...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28726484/annals-express-experience-with-newer-central-nervous-system-autoantibodies
#9
Abid Karim, Saiju Jacob
In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic Glutamate receptors (NMDAR, AMPAR), metabotropic Glutamate receptors (mGluR1 and mGluR5), voltage gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against Glycine receptor, Glutamic acid decarboxylase (GAD), Gamma Amino Butyric Acid B (GABAB), Dopamine-2-receptor (D2R) and Dipeptidyl-peptidase-like protein 6 (DPPX)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28725974/carbofuran-causes-neuronal-vulnerability-to-glutamate-by-decreasing-glua2-protein-levels-in-rat-primary-cortical-neurons
#10
Kanae Umeda, Masatsugu Miyara, Keishi Ishida, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Glutamate receptor 2 (GluA2/GluR2) is one of the four subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR); an increase in GluA2-lacking AMPARs contributes to neuronal vulnerability to excitotoxicity because of the receptor's high Ca(2+) permeability. Carbofuran is a carbamate pesticide used in agricultural areas to increase crop productivity. Due to its broad-spectrum action, carbofuran has also been used as an insecticide, nematicide, and acaricide. In this study, we investigated the effect of carbofuran on GluA2 protein expression...
July 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28725942/l-arginine-supplementation-prevents-allodynia-and-hyperalgesia-in-painful-diabetic-neuropathic-rats-by-normalizing-plasma-nitric-oxide-concentration-and-increasing-plasma-agmatine-concentration
#11
Lusliany J Rondón, M C Farges, N Davin, B Sion, A M Privat, M P Vasson, A Eschalier, C Courteix
PURPOSE: Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes...
July 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28725181/impact-of-proestrus-on-gene-expression-in-the-medial-preoptic-area-of-mice
#12
Csaba Vastagh, Zsolt Liposits
The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that-via wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28720382/activated-leukocyte-cell-adhesion-molecule-is-involved-in-excitatory-synaptic-transmission-and-plasticity-in-the-rat-spinal-dorsal-horn
#13
Eun-Sung Park, Sang-Min Jeon, Haein Weon, Hee-Jung Cho, Dong-Ho Youn
Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH...
July 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#14
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28719878/the-effects-of-fluoride-on-neuronal-function-occurs-via-cytoskeleton-damage-and-decreased-signal-transmission
#15
Lingli Chen, Hongmei Ning, Zhihong Yin, Xiaochao Song, Yongchao Feng, Hao Qin, Yi Li, Jundong Wang, Yaming Ge, Wenkui Wang
It has been reported that fluoride exposure may cause serious public health problems, particularly neurotoxicity. However, the underlying mechanisms remain unclear. This study used Neuro-2A cells to investigate the effects of fluoride on the cytoskeleton. The Neuro-2A cells were exposed to 0, 1, 2, 4 and 6 mM sodium fluoride (NaF) for 24 h. Cell viability and lactate dehydrogenase (LDH) release were examined. It was observed that exposure to NaF reduced cell viability, disrupted cellular membrane integrity, and high levels of LDH were released...
June 30, 2017: Chemosphere
https://www.readbyqxmd.com/read/28719803/elevated-sterol-regulatory-elementary-binding-protein-1-and-glua2-levels-in-the-hippocampal-nuclear-fraction-of-genetic-absence-epilepsy-rats-from-strasbourg
#16
Sathiya Sekar, Entesar Omran, Venkat Gopalakrishnan, John G Howland, Terrance P Snutch, Changiz Taghibiglou
Studies in animal models and human tissues show that nuclear translocation of sterol regulatory element binding protein 1 (SREBP1) and glutamate A2 subunit (GluA2) of cell-surface AMPA receptor (AMPAR) trigger neuronal excitotoxicity-induced apoptosis in stroke. However, it is not known whether a similar type of underlying pathophysiology occurs in absence epilepsy. To explore this issue, we examined the levels of mature SREBP1, GluA2, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), p53, and activated to total caspase 3 ratio in nuclear fractions (NF) of hippocampal homogenate from 8 to 10 week old male Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and non-epileptic control (NEC) strains...
July 12, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#17
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#18
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716937/altered-metabotropic-glutamate-receptor-5-markers-in-ptsd-in-vivo-and-postmortem-evidence
#19
Sophie E Holmes, Matthew J Girgenti, Margaret T Davis, Robert H Pietrzak, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Steven Southwick, Ronald S Duman, Richard E Carson, John H Krystal, Irina Esterlis
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [(18)F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28715108/ivermectin-activates-girk-channels-in-a-pip2-dependent-g%C3%AE-%C3%AE-independent-manner-and-an-amino-acid-residue-at-the-slide-helix-governs-the-activation
#20
I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate-gated Cl(-) channel in parasites. It is also known that IVM binds to the transmembrane domains (TMs) of several ligand-gated channels, such as Cys-loop receptors and P2X receptors. In this study, we found that the G-protein-gated inwardly rectifying K(+) (GIRK) channel is activated by IVM directly. By electrophysiological recordings in Xenopus oocytes, we observed that IVM activates GIRK channel in a phosphatidylinositol-4,5-biphosphate (PIP2 )-dependent manner, and that the IVM-mediated GIRK activation is independent of Gβγ ...
July 17, 2017: Journal of Physiology
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