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https://www.readbyqxmd.com/read/29337309/role-for-vglut2-in-selective-vulnerability-of-midbrain-dopamine-neurons
#1
Thomas Steinkellner, Vivien Zell, Zachary J Farino, Mark S Sonders, Michael Villeneuve, Robin J Freyberg, Serge Przedborski, Wei Lu, Zachary Freyberg, Thomas S Hnasko
Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice...
February 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29324300/hippocampal-insulin-resistance-links-maternal-obesity-with-impaired-neuronal-plasticity-in-adult-offspring
#2
Lisa Schmitz, Rebecca Kuglin, Inga Bae-Gartz, Ruth Janoschek, Sarah Appel, Andrea Mesaros, Igor Jakovcevski, Christina Vohlen, Marion Handwerk, Regina Ensenauer, Jörg Dötsch, Eva Hucklenbruch-Rother
OBJECTIVE: Maternal obesity and a disturbed metabolic environment during pregnancy and lactation have been shown to result in many long-term health consequences for the offspring. Among them, impairments in neurocognitive development and performance belong to the most dreaded ones. So far, very few mechanistic approaches have aimed to determine the responsible molecular events. METHODS: In a mouse model of maternal diet-induced obesity and perinatal hyperinsulinemia, we assessed adult offspring's hippocampal insulin signaling as well as concurrent effects on markers of hippocampal neurogenesis, synaptic plasticity and function using western blotting and immunohistochemistry...
December 28, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29298905/gliotransmission-beyond-black-and-white
#3
Iaroslav Savtchouk, Andrea Volterra
Astrocytes are highly complex cells with many emerging putative roles in brain function. Of these, gliotransmission (active information transfer from glia to neurons) has probably the widest implications on our understanding of how the brain works: do astrocytes really contribute to information processing within the neural circuitry? "Positive evidence" for this stems from work of multiple laboratories reporting many examples of modulatory chemical signaling from astrocytes to neurons in the timeframe of hundreds of milliseconds to several minutes...
January 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29291238/developmental-emergence-of-phenotypes-in-the-auditory-brainstem-nuclei-of-fmr1-knockout-mice
#4
Sarah E Rotschafer, Karina S Cramer
Fragile X syndrome (FXS), the most common monogenic cause of autism, is often associated with hypersensitivity to sound. Several studies have shown abnormalities in the auditory brainstem in FXS; however, the emergence of these auditory phenotypes during development has not been described. Here, we investigated the development of phenotypes in FXS model [Fmr1 knockout (KO)] mice in the ventral cochlear nucleus (VCN), medial nucleus of the trapezoid body (MNTB), and lateral superior olive (LSO). We studied features of the brainstem known to be altered in FXS or Fmr1 KO mice, including cell size and expression of markers for excitatory (VGLUT) and inhibitory (VGAT) synapses...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29273736/vglut1-functions-as-a-glutamate-proton-exchanger-with-chloride-channel-activity-in-hippocampal-glutamatergic-synapses
#5
Magalie Martineau, Raul E Guzman, Christoph Fahlke, Jürgen Klingauf
Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely unknown. Here, we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in SVs VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29199069/vglut1-binding-to-endophilin-or-intersectin1-and-dynamin-phosphorylation-in-a-diurnal-context
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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