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https://www.readbyqxmd.com/read/29331845/effect-of-levetiracetam-on-extracellular-amino-acid-levels-in-the-dorsal-hippocampus-of-rats-with-temporal-lobe-epilepsy
#1
Pichardo Macías Luz Adriana, Ramírez Mendiola Blanca Alcira, Contreras García Itzel Jatziri, Zamudio Hernández Sergio Roberto, Chávez Pacheco Juan Luis, Sánchez Huerta Karla Berenice, Mendoza Torreblanca Julieta Griselda
Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29328916/the-neuronal-gene-arc-encodes-a-repurposed-retrotransposon-gag-protein-that-mediates-intercellular-rna-transfer
#2
Elissa D Pastuzyn, Cameron E Day, Rachel B Kearns, Madeleine Kyrke-Smith, Andrew V Taibi, John McCormick, Nathan Yoder, David M Belnap, Simon Erlendsson, Dustin R Morado, John A G Briggs, Cédric Feschotte, Jason D Shepherd
The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328915/retrovirus-like-gag-protein-arc1-binds-rna-and-traffics-across-synaptic-boutons
#3
James Ashley, Benjamin Cordy, Diandra Lucia, Lee G Fradkin, Vivian Budnik, Travis Thomson
Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328021/the-presynaptic-ribbon-maintains-vesicle-populations-at-the-hair-cell-afferent-fiber-synapse
#4
Lars Becker, Michael E Schnee, Mamiko Niwa, Willy Sun, Stephan Maxeiner, Sara Talaei, Bechara Kachar, Mark A Rutherford, Anthony J Ricci
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; high stimulus level rescued exocytosis in KO...
January 12, 2018: ELife
https://www.readbyqxmd.com/read/29328020/the-synaptic-ribbon-is-critical-for-sound-encoding-at-high-rates-and-with-temporal-precision
#5
Philippe Jean, David Lopez de la Morena, Susann Michanski, Lina María Jaime Tobón, Rituparna Chakrabarti, Maria Magdalena Picher, Jakob Neef, SangYong Jung, Mehmet Gültas, Stephan Maxeiner, Andreas Neef, Carolin Wichmann, Nicola Strenzke, Chad Grabner, Tobias Moser
We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment...
January 12, 2018: ELife
https://www.readbyqxmd.com/read/29326174/muscle-nicotinic-acetylcholine-receptors-may-mediate-trans-synaptic-signaling-at-the-mouse-neuromuscular-junction
#6
Xueyong Wang, J Michael McIntosh, Mark M Rich
Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction of male and female mice, triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29323161/lack-of-fgf18-causes-abnormal-clustering-of-motor-nerve-terminals-at-the-neuromuscular-junction-with-reduced-acetylcholine-receptor-clusters
#7
Kenyu Ito, Bisei Ohkawara, Hideki Yagi, Hiroaki Nakashima, Mikito Tsushima, Kyotaro Ota, Hiroyuki Konishi, Akio Masuda, Shiro Imagama, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18-/- mice at E18...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319803/down-regulation-of-glutamate-release-from-hippocampal-neurons-by-sialidase
#8
Minami Akira, Ami Ishii, Sumika Shimba, Takahiro Kano, Eri Fujioka, Saki Sai, Nagisa Oshio, Sayaka Ishibashi, Tadanobu Takahashi, Yuuki Kurebayashi, Hiroaki Kanazawa, Nobuhiro Yuki, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase, which removes sialic acid residues in sialylglycoconjugates, is essential for hippocampal memory and synaptic plasticity. Enzyme activity of sialidase is rapidly increased in response to neural excitation. Because sialic acid bound to gangliosides such as the tetra-sialoganglioside GQ1b is crucial for calcium signaling and neurotransmitter release, neural activity-dependent removal of sialic acid may affect hippocampal neurotransmission. In the present study, we found that 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA), a sialidase inhibitor, increased expression of ganglioside GQ1b/GT1a in hippocampal acute slices...
January 8, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29317246/presynaptic-calcium-channels
#9
REVIEW
Sumiko Mochida
At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca2+ entry through voltage-gated Ca2+ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca2+ channels form a large signaling complex, which targets synaptic vesicles to Ca2+ channels for efficient release and mediates Ca2+ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation...
January 6, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29316491/presynaptic-endocytic-factors-in-autophagy-and-neurodegeneration
#10
REVIEW
Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration...
January 6, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29311144/differentiation-and-characterization-of-excitatory-and-inhibitory-synapses-by-cryo-electron-tomography-and-correlative-microscopy
#11
Chang-Lu Tao, Yun-Tao Liu, Rong Sun, Bin Zhang, Lei Qi, Sakar Shivakoti, Chong-Li Tian, Peijun Zhang, Pak-Ming Lau, Z Hong Zhou, Guo-Qiang Bi
As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ three-dimensional organization of synaptic organelles and macromolecules in their native state...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29303480/a-postsynaptic-pi3k-cii-dependent-signaling-controller-for-presynaptic-homeostatic-plasticity
#12
Anna G Hauswirth, Kevin J Ford, Tingting Wang, Richard D Fetter, Amy Tong, Graeme W Davis
Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP...
January 5, 2018: ELife
https://www.readbyqxmd.com/read/29302779/glia-to-neuron-transfer-of-mirnas-via-extracellular-vesicles-a-new-mechanism-underlying-inflammation-induced-synaptic-alterations
#13
Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic spine formation and synaptic stability...
January 4, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29295857/defects-in-synaptic-transmission-at-the-neuromuscular-junction-precedes-motor-deficits-in-a-tdp-43q331k-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis
#14
Kirat K Chand, Kah Meng Lee, John D Lee, Hao Qiu, Emily F Willis, Nickolas A Lavidis, Massimo A Hilliard, Peter G Noakes
Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43Q331K mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295581/prevention-of-synaptic-alterations-and-neurotoxic-effects-of-pamam-dendrimers-by-surface-functionalization
#15
Felipe Vidal, Pilar Vásquez, Francisca R Cayumán, Carola Díaz, Jorge Fuentealba, Luis G Aguayo, Gonzalo E Yévenes, Joel Alderete, Leonardo Guzmán
One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM) dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4) in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25) and polyethylene glycol (PPEG25)...
December 25, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29289693/manganese-induced-alpha-synuclein-overexpression-impairs-synaptic-vesicle-fusion-by-disrupting-the-rab3-cycle-in-primary-cultured-neurons
#16
Tong-Yu Wang, Zhuo Ma, Can Wang, Chang Liu, Dong-Ying Yan, Yu Deng, Wei Liu, Zhao-Fa Xu, Bin Xu
Overexposure to Manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether Mn-induced alpha-synuclein protein overexpression could disrupt the Rab3 cycle leading to synaptic vesicle fusion dysfunction. After the neurons were exposed to Mn (100 μM) for 0, 6, 12, 24 h, [Ca2+]i, alpha-synuclein and Rab3A-GTP protein expression increased gradually...
December 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29288152/cytotoxic-granule-endocytosis-depends-on-the-flower-protein
#17
Hsin-Fang Chang, Stefanie Mannebach, Andreas Beck, Keerthana Ravichandran, Elmar Krause, Katja Frohnweiler, Claudia Fecher-Trost, Claudia Schirra, Varsha Pattu, Veit Flockerzi, Jens Rettig
Cytotoxic T lymphocytes (CTLs) kill target cells by the regulated release of cytotoxic substances from granules at the immunological synapse. To kill multiple target cells, CTLs use endocytosis of membrane components of cytotoxic granules. We studied the potential calcium dependence of endocytosis in mouse CTLs on Flower, which mediates the calcium dependence of synaptic vesicle endocytosis in Drosophila melanogaster Flower is predominantly localized on intracellular vesicles that move to the synapse on target cell contact...
December 29, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29287214/favorable-adverse-effect-profile-of-brivaracetam-vs-levetiracetam-in-a-preclinical-model
#18
Nathalie T Sanon, Jonathan Gagné, Daniele C Wolf, Soumia Aboulamer, Ciprian M Bosoi, Alexe Simard, Estelle Messiet, Sébastien Desgent, Lionel Carmant
Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors...
December 26, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29284749/visualizing-long-term-single-molecule-dynamics-in-vivo-by-stochastic-protein-labeling
#19
Hui Liu, Peng Dong, Maria S Ioannou, Li Li, Jamien Shea, H Amalia Pasolli, Jonathan B Grimm, Patricia K Rivlin, Luke D Lavis, Minoru Koyama, Zhe Liu
Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies of labeled molecules within the resolution limit. Here we devise a universal genetic strategy to precisely control copy number of fluorescently labeled molecules in a cell. This system has a dynamic range of ∼10,000-fold, enabling sparse labeling of proteins expressed at different abundance levels. Combined with photostable labels, this system extends the duration of automated single-molecule tracking by two orders of magnitude...
December 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29284679/mesenchymal-stem-cells-and-cell-derived-extracellular-vesicles-protect-hippocampal-neurons-from-oxidative-stress-and-synapse-damage-induced-by-amyloid-%C3%AE-oligomers
#20
Mariana A de Godoy, Leonardo M Saraiva, Luiza R P Carvalho, Andreia Vasconcelos-Dos-Santos, Hellen J V Beiral, Alane Bernardo Ramos, Livian R de Paula Silva, Renata B Leal, Victor H S Monteiro, Carolina V Braga, Carlla A de Araujo-Silva, Leandro C Sinis, Victor Bodart Santos, Tais Hanae Kasai Brunswick, Carolina de Lima Alcantara, Ana Paula C A Lima, Narcisa L da Cunha E Silva, Antonio Galina, Adalberto Vieyra, Fernanda G De Felice, Rosalia Mendez-Otero, Sergio T Ferreira
Alzheimer disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-beta peptide (AβOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AβOs on hippocampal neurons...
December 28, 2017: Journal of Biological Chemistry
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