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https://www.readbyqxmd.com/read/29199069/vglut1-binding-to-endophilin-or-intersectin1-and-dynamin-phosphorylation-in-a-diurnal-context
#1
Karin Richter, Isabelle Schmutz, Mahesh Darna, Johannes-F Zander, Rohit Chavan, Urs Albrecht, Gudrun Ahnert-Hilger
Glutamate is concentrated into synaptic vesicles (SV) by the vesicular glutamate transporters (VGLUT) 1and 2. VGLUTs also harbour a Na+/Pi -transport activity when residing at the plasma membrane. Here we aimed to identify whether the diurnal switches of VGLUT1 parallels interactions with or modification of endocytic proteins VGLUT1 and dynamin bind to SH3 domains of either endophilin (Enph) or intersectin 1 (ITSN1) harbouring one or five SH3 domains A-E, respectively. We followed diurnal variations by pull down experiments using SH3 fusion protein and brains from mice entrained in a strict 24 h light dark cycle (12 h light Zeitgeber (ZT) 0, 6; 12 h dark ZT 12 and 18)...
November 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/29160768/diverse-modes-of-synaptic-signaling-regulation-and-plasticity-distinguish-classes-of-c-elegans-glutamatergic-neurons
#2
Donovan Ventimiglia, Cornelia I Bargmann
Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWC(ON) and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWC(ON) is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWC(ON) release relies upon UNC-18 and on the protein kinase C homolog PKC-1...
November 21, 2017: ELife
https://www.readbyqxmd.com/read/29123471/vglut2-trafficking-is-differentially-regulated-by-adaptor-proteins-ap-1-and-ap-3
#3
Haiyan Li, Magda S Santos, Chihyung K Park, Yuriy Dobry, Susan M Voglmaier
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29101523/functional-comparison-of-corticostriatal-and-thalamostriatal-postsynaptic-responses-in-striatal-neurons-of-the-mouse
#4
M A Arias-García, D Tapia, J A Laville, V M Calderón, Y Ramiro-Cortés, J Bargas, E Galarraga
Synaptic inputs from cortex and thalamus were compared in electrophysiologically defined striatal cell classes: direct and indirect pathways' striatal projection neurons (dSPNs and iSPNs), fast-spiking interneurons (FS), cholinergic interneurons (ChINs), and low-threshold spiking-like (LTS-like) interneurons. Our purpose was to observe whether stimulus from cortex or thalamus had equivalent synaptic strength to evoke prolonged suprathreshold synaptic responses in these neuron classes. Subthreshold responses showed that inputs from either source functionally mix up in their dendrites at similar electrotonic distances from their somata...
November 3, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29091932/essential-roles-of-aspartate-aminotransferase-1-and-vesicular-glutamate-transporters-in-%C3%AE-cell-glutamate-signaling-for-incretin-induced-insulin-secretion
#5
Naoya Murao, Norihide Yokoi, Kohei Honda, Guirong Han, Tomohide Hayami, Ghupurjan Gheni, Harumi Takahashi, Kohtaro Minami, Susumu Seino
Incretins (GLP-1 and GIP) potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS) that requires two critical processes: 1) generation of cytosolic glutamate through the malate-aspartate (MA) shuttle in glucose metabolism and 2) glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1), a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively), which participate in glutamate transport into secretory vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/29066956/cell-type-specific-expression-of-corticotropin-releasing-hormone-binding-protein-in-gabaergic-interneurons-in-the-prefrontal-cortex
#6
Kyle D Ketchesin, Nicholas S Huang, Audrey F Seasholtz
Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28859339/pathologic-involvement-of-glutamatergic-striatal-inputs-from-the-cortices-in-tar-dna-binding-protein-43%C3%A2-kda-related-frontotemporal-lobar-degeneration-and-amyotrophic-lateral-sclerosis
#7
Yuichi Riku, Hirohisa Watanabe, Mari Yoshida, Maya Mimuro, Yasushi Iwasaki, Michihito Masuda, Shinsuke Ishigaki, Masahisa Katsuno, Gen Sobue
In frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), recent studies have presumed relationships between cognitive declines and striatal dysfunctions. The striatum contributes to socio-cognitive functions by receiving glutamatergic inputs from the cerebral cortices. However, the vulnerability of these cortico-striatal inputs is unclear in these diseases. This study aimed to evaluate the glutamatergic inputs to the striatum from the cerebral cortices in patients with sporadic TDP-43-related FTLD (FTLD-TDP) and ALS (ALS-TDP)...
September 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28776199/contribution-of-vesicular-glutamate-transporters-to-stress-response-and-related-psychopathologies-studies-in-vglut3-knockout-mice
#8
REVIEW
Hanga Réka Horváth, Csilla Lea Fazekas, Diána Balázsfi, Subodh Kumar Jain, József Haller, Dóra Zelena
Maintenance of the homeostasis in a constantly changing environment is a fundamental process of life. Disturbances of the homeostatic balance is defined as stress response and is induced by wide variety of challenges called stressors. Being the main excitatory neurotransmitter of the central nervous system glutamate is important in the adaptation process of stress regulating both the catecholaminergic system and the hypothalamic-pituitary-adrenocortical axis. Data are accumulating about the role of different glutamatergic receptors at all levels of these axes, but little is known about the contribution of different vesicular glutamate transporters (VGluT1-3) characterizing the glutamatergic neurons...
August 3, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28731329/generation-and-characterization-of-anti-vglut-nanobodies-acting-as-inhibitors-of-transport
#9
COMPARATIVE STUDY
Stephan Schenck, Laura Kunz, Daniela Sahlender, Els Pardon, Eric R Geertsma, Iaroslav Savtchouk, Toshiharu Suzuki, Yvonne Neldner, Saša Štefanić, Jan Steyaert, Andrea Volterra, Raimund Dutzler
The uptake of glutamate by synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). The central role of these transporters in excitatory neurotransmission underpins their importance as pharmacological targets. Although several compounds inhibit VGLUTs, highly specific inhibitors were so far unavailable, thus limiting applications to in vitro experiments. Besides their potential in pharmacology, specific inhibitors would also be beneficial for the elucidation of transport mechanisms. To overcome this shortage, we generated nanobodies (Nbs) by immunization of a llama with purified rat VGLUT1 and subsequent selection of binders from a phage display library...
August 1, 2017: Biochemistry
https://www.readbyqxmd.com/read/28669028/the-excitatory-inhibitory-input-to-orexin-hypocretin-neuron-soma-undergoes-day-night-reorganization
#10
Claudia Laperchia, Roberta Imperatore, Idris A Azeez, Federico Del Gallo, Giuseppe Bertini, Gigliola Grassi-Zucconi, Luigia Cristino, Marina Bentivoglio
Orexin (OX)/hypocretin-containing neurons are main regulators of wakefulness stability, arousal, and energy homeostasis. Their activity varies in relation to the animal's behavioral state. We here tested whether such variation is subserved by synaptic plasticity phenomena in basal conditions. Mice were sacrificed during day or night, at times when sleep or wake, respectively, predominates, as assessed by electroencephalography in matched mice. Triple immunofluorescence was used to visualize OX-A perikarya and varicosities containing the vesicular glutamate transporter (VGluT)2 or the vesicular GABA transporter (VGAT) combined with synaptophysin (Syn) as a presynaptic marker...
July 1, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28607372/enhanced-derivation-of-human-pluripotent-stem-cell-derived-cortical-glutamatergic-neurons-by-a-small-molecule
#11
Shi-Ying Cao, Yao Hu, Cheng Chen, Fang Yuan, Min Xu, Qi Li, Kai-Heng Fang, Yaoyu Chen, Yan Liu
Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28493916/vesicular-glutamate-transporters-play-a-role-in-neuronal-differentiation-of-cultured-svz-derived-neural-precursor-cells
#12
Eduardo H Sánchez-Mendoza, Victor Bellver-Landete, Carmen Arce, Thorsten R Doeppner, Dirk M Hermann, María Jesús Oset-Gasque
The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes...
2017: PloS One
https://www.readbyqxmd.com/read/28442357/dl-3-n-butylphthalide-promotes-neuroplasticity-and-motor-recovery-in-stroke-rats
#13
Yefei Sun, Xi Cheng, Huibin Wang, Xiaopeng Mu, Yifan Liang, YuJia Luo, Huiling Qu, Chuansheng Zhao
BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks...
June 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#14
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314816/characterization-of-a-human-point-mutation-of-vglut3-p-a211v-in-the-rodent-brain-suggests-a-nonuniform-distribution-of-the-transporter-in-synaptic-vesicles
#15
Lauriane Ramet, Johannes Zimmermann, Tiphaine Bersot, Odile Poirel, Stéphanie De Gois, Katlin Silm, Diana Yae Sakae, Nina Mansouri-Guilani, Marie-Josée Bourque, Louis-Eric Trudeau, Nicolas Pietrancosta, Stéphanie Daumas, Véronique Bernard, Christian Rosenmund, Salah El Mestikawy
The atypical vesicular glutamate transporter type 3 (VGLUT3) is expressed by subpopulations of neurons using acetylcholine, GABA, or serotonin as neurotransmitters. In addition, VGLUT3 is expressed in the inner hair cells of the auditory system. A mutation (p.A211V) in the gene that encodes VGLUT3 is responsible for progressive deafness in two unrelated families. In this study, we investigated the consequences of the p.A211V mutation in cell cultures and in the CNS of a mutant mouse. The mutation substantially decreased VGLUT3 expression (-70%)...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28294308/neuronal-inhibition-and-seizure-suppression-by-acetoacetate-and-its-analog-2-phenylbutyrate
#16
Atsushi Kadowaki, Nagisa Sada, Narinobu Juge, Ayaka Wakasa, Yoshinori Moriyama, Tsuyoshi Inoue
OBJECTIVE: The ketogenic diet is clinically used to treat drug-resistant epilepsy. The diet treatment markedly increases ketone bodies (acetoacetate and β-hydroxybutyrate), which work as energy metabolites in the brain. Here, we investigated effects of acetoacetate on voltage-dependent Ca(2+) channels (VDCCs) in pyramidal cells of the hippocampus. We further explored an acetoacetate analog that inhibited VDCCs in pyramidal cells, reduced excitatory postsynaptic currents (EPSCs), and suppressed seizures in vivo...
May 2017: Epilepsia
https://www.readbyqxmd.com/read/28286184/altered-functional-efficacy-of-hippocampal-interneuron-during-epileptogenesis-following-febrile-seizures
#17
Yeon Hee Yu, Kahyun Lee, Dal Sik Sin, Kyung-Ho Park, Dae-Kyoon Park, Duk-Soo Kim
Febrile seizure (FS) is the most common seizure type in infants and young children. FS may induce functional changes in the hippocampal circuitries. Abnormality of excitatory and inhibitory neurotransmissions was previously related to wide-spread seizure attack in the hippocampus following recurrent seizure onset. To clarify the involvement of expressional changes and functional alterations of hippocampal interneurons with epileptogenesis following FS, we investigated long-term effects following recurrent seizure in a hyperthermia-induced seizure animal model...
March 7, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28255754/vesicular-glutamate-transporter-inhibitors-structurally-modified-brilliant-yellow-analogs
#18
Jason Kehrl, J Christian Althaus, Hollis D Showalter, DiAndra M Rudzinski, Michael A Sutton, Tetsufumi Ueda
Glutamate uptake into synaptic vesicles in nerve terminals is a pivotal step in glutamate synaptic transmission. Glutamate is the major excitatory neurotransmitter and, as such, the vesicular glutamate transporter (VGLUT) responsible for this uptake is involved in a variety of nervous system functions and various types of pathophysiology. As yet, no VGLUT-specific, membrane-permeable agents have been developed to affect neuronal function in intact neurons, although two potent VGLUTspecific inhibitors are known...
June 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28193459/epileptiform-activity-and-behavioral-arrests-in-mice-overexpressing-the-calcium-channel-subunit-%C3%AE-2%C3%AE-1
#19
Leonardo C Faria, Feng Gu, Isabel Parada, Ben Barres, Z David Luo, David A Prince
The alpha2delta-1 subunit (α2δ-1) of voltage-gated calcium channels is a receptor for astrocyte-secreted thrombospondins that promote developmental synaptogenesis. Alpha2delta-1 receptors are upregulated in models of injury-induced peripheral pain and epileptogenic neocortical trauma associated with an enhancement of excitatory synaptic connectivity. These results lead to the hypothesis that overexpression of α2δ-1 alone in neocortex of uninjured transgenic (TG) mice might result in increased excitatory connectivity and consequent cortical hyperexcitability and epileptiform activity...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28188742/function-and-expression-of-a-splicing-variant-of-vesicular-glutamate-transporter-1
#20
Satomi Moriyama, Masafumi Iharada, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa
Vesicular glutamate transporter (VGLUT) is an active transporter responsible for vesicular storage of glutamate in synaptic vesicles and plays an essential role in glutamatergic neurotransmission. VGLUT consists of three isoforms, VGLUT1, VGLUT2, and VGLUT3. The VGLUT1 variant, VGLUT1v, with an additional 75-base pair sequence derived from a second intron between exons 2 and 3, which corresponds to 25 amino acid residues in the 1st loop of VGLUT1, is the only splicing variant among VGLUTs, although whether VGLUT1v protein is actually translated at the protein level remains unknown...
May 2017: Biochimica et Biophysica Acta
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