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Frontiers in Molecular Neuroscience

Bo-Zong Shao, Qi Cao, Chong Liu
Central nervous system (CNS) is one of the largest killers of people's health all over the world. The overactivation of the immune and inflammatory responses is considered as an important factor, contributing to the pathogenesis and progression of CNS disorders. Among all kinds of immune and inflammatory reaction, the inflammasome, a complex of proteins, has been drawn increasingly attention to by researchers. The initiation and activation of the inflammasome is involved in the onset of various kinds of diseases...
2018: Frontiers in Molecular Neuroscience
Ana Rita Costa, Rita Pinto-Costa, Sara Castro Sousa, Mónica Mendes Sousa
In the adult nervous system axon caliber varies widely amongst different tracts. When considering a given axon, its diameter can further fluctuate in space and time, according to processes including the distribution of organelles and activity-dependent mechanisms. In addition, evidence is emerging supporting that in axons circumferential tension/contractility is present. Axonal diameter is generically regarded as being regulated by neurofilaments. When neurofilaments are absent or low, microtubule-dependent mechanisms can also contribute to the regulation of axon caliber...
2018: Frontiers in Molecular Neuroscience
Sebastian Hofer, Katharina Kainz, Andreas Zimmermann, Maria A Bauer, Tobias Pendl, Michael Poglitsch, Frank Madeo, Didac Carmona-Gutierrez
Huntington's disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the huntingtin protein, which harbors an elongated polyglutamine domain and is highly prone to aggregation. However, many aspects underlying the cytotoxicity of mutant huntingtin (mHTT) remain elusive, hindering the efficient development of applicable interventions to counteract HD...
2018: Frontiers in Molecular Neuroscience
Yuanyi Xie, Xu-Feng Huang
No abstract text is available yet for this article.
2018: Frontiers in Molecular Neuroscience
Nicolás M Rosas, Anabel Alvarez Juliá, Sofia E Alzuri, Alberto C Frasch, Beata Fuchsova
Neuronal membrane glycoprotein M6a (Gpm6a) is a protein with four transmembrane regions and the N- and the C-ends facing the cytosol. It functions in processes of neuronal development, outgrowth of neurites, and formation of filopodia, spines, and synapsis. Molecular mechanisms by which Gpm6a acts in these processes are not fully comprehended. Structural similarities of Gpm6a with tetraspanins led us to hypothesize that, similarly to tetraspanins, the cytoplasmic tails function as connections with cytoskeletal and/or signaling proteins...
2018: Frontiers in Molecular Neuroscience
Raffaella Morini, Silvia Ferrara, Fabio Perrucci, Stefania Zambetti, Silvia Pelucchi, Elena Marcello, Fabrizio Gardoni, Flavia Antonucci, Michela Matteoli, Elisabetta Menna
Actin-based remodeling underlines spine morphogenesis and plasticity and is crucially involved in the processes that constantly reshape the circuitry of the adult brain in response to external stimuli, leading to learning and memory formation and supporting cognitive functions. Hence spine morphology and synaptic strength are tightly linked and indeed abnormalities in spine number and morphology have been described in a number of neurological disorders such as autism spectrum disorders (ASDs), schizophrenia and intellectual disabilities...
2018: Frontiers in Molecular Neuroscience
Rafael Vitor Lima da Cruz, Thiago C Moulin, Lyvia Lintzmaier Petiz, Richardson N Leão
The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation...
2018: Frontiers in Molecular Neuroscience
Noga Gershoni-Emek, Topaz Altman, Ariel Ionescu, Christopher J Costa, Tal Gradus-Pery, Dianna E Willis, Eran Perlson
Local protein synthesis in neuronal axons plays an important role in essential spatiotemporal signaling processes; however, the molecular basis for the post-transcriptional regulation controlling this process in axons is still not fully understood. Here we studied the axonal mechanisms underlying the transport and localization of microRNA (miRNA) and the RNAi machinery along the axon. We first identified miRNAs, Dicer, and Argonaute-2 (Ago2) in motor neuron (MN) axons. We then studied the localization of RNAi machinery and demonstrated that mitochondria associate with miR-124 and RNAi proteins in axons...
2018: Frontiers in Molecular Neuroscience
Nadine Kerr, Marta García-Contreras, Sam Abbassi, Nancy H Mejias, Brandon R Desousa, Camillo Ricordi, W Dalton Dietrich, Robert W Keane, Juan Pablo de Rivero Vaccari
The inflammasome is a key contributor to the inflammatory innate immune response after stroke. We have previously shown that inflammasome proteins are released in extracellular vesicles (EV) after brain and spinal cord injury. In addition, we have shown that inflammasome proteins offer great promise as biomarkers of central nervous system (CNS) injury following brain trauma. In the present study, we used a Simple Plex Assay (Protein Simple), a novel multi-analyte automated microfluidic immunoassay platform, to analyze serum and serum-derived EV samples from stroke patients and control subjects for inflammasome protein levels of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), Interleukins (IL)-1β, and (IL)-18...
2018: Frontiers in Molecular Neuroscience
Roberta Schellino, Marina Boido, Tiziana Borsello, Alessandro Vercelli
Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that occurs in early childhood. The disease is caused by the deletion/mutation of the survival motor neuron 1 (SMN1) gene resulting in progressive skeletal muscle atrophy and paralysis, due to the degeneration of spinal motor neurons (MNs). Currently, the cellular and molecular mechanisms underlying MN death are only partly known, although recently it has been shown that the c-Jun NH2 -terminal kinase (JNK)-signaling pathway might be involved in the SMA pathogenesis...
2018: Frontiers in Molecular Neuroscience
Christoph Wolf, Agnes Weth, Sebastian Walcher, Christian Lax, Werner Baumgartner
While the numerous influences of synaptically released zinc on synaptic efficiency during long-term potentiation have been discussed by many authors already, we focused on the possible effect of zinc on cadherins and therefore its contribution to morphological changes in the context of synaptic plasticity. The difficulty with gaining insights into the dynamics of zinc-cadherin interaction is the inability to directly observe it on a suitable timescale. Therefore our approach was to establish an analytical model of the zinc diffusion dynamics in the synaptic cleft and experimentally validate, if the theoretical concentrations at the periphery of the synaptic cleft are sufficient to significantly modulate cadherin-mediated adhesion...
2018: Frontiers in Molecular Neuroscience
Ismail Ben Soussia, Frank S Choveau, Sandy Blin, Eun-Jin Kim, Sylvain Feliciangeli, Franck C Chatelain, Dawon Kang, Delphine Bichet, Florian Lesage
TREK/TRAAK channels are polymodal K+ channels that convert very diverse stimuli, including bioactive lipids, mechanical stretch and temperature, into electrical signals. The nature of the structural changes that regulate their activity remains an open question. Here, we show that a cytoplasmic domain (the proximal C-ter domain, pCt) exerts antagonistic effects in TREK1 and TRAAK. In basal conditions, pCt favors activity in TREK1 whereas it impairs TRAAK activity. Using the conformation-dependent binding of fluoxetine, we show that TREK1 and TRAAK conformations at rest are different, and under the influence of pCt...
2018: Frontiers in Molecular Neuroscience
Rafael Franco, David Aguinaga, Irene Reyes, Enric I Canela, Jaume Lillo, Airi Tarutani, Masato Hasegawa, Anna Del Ser-Badia, José A Del Rio, Michael R Kreutz, Carlos A Saura, Gemma Navarro
N -methyl-D-aspartate receptors (NMDARs) respond to glutamate to allow the influx of calcium ions and the signaling to the mitogen-activated protein kinase (MAPK) cascade. Both MAPK- and Ca2+ -mediated events are important for both neurotransmission and neural cell function and fate. Using a heterologous expression system, we demonstrate that NMDAR may interact with the EF-hand calcium-binding proteins calmodulin, calneuron-1, and NCS1 but not with caldendrin. NMDARs were present in primary cultures of both neurons and microglia from cortex and hippocampus...
2018: Frontiers in Molecular Neuroscience
Mei-Xue Dong, Xia Feng, Xiao-Min Xu, Ling Hu, Yang Liu, Si-Yu Jia, Bo Li, Wei Chen, You-Dong Wei
Depression is a common comorbidity in Parkinson's disease (PD) but is underdiagnosed. We aim to investigate the altered metabolic pathways of Parkinson's disease-related depression (PDD) in plasma and to identify potential biomarkers for clinical diagnosis. Consecutive patients with PD were recruited, clinically assessed, and patients with PDD identified. Fasting plasma samples were collected from 99 patients and differentially expressed metabolites and proteins between patients with PDD and PD were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics analysis, followed by an integrated analysis...
2018: Frontiers in Molecular Neuroscience
Chunmei Jin, Hyojin Kang, Jae Ryun Ryu, Shinhyun Kim, Yinhua Zhang, Yeunkum Lee, Yoonhee Kim, Kihoon Han
Variants of the SH3 and multiple ankyrin repeat domain 3 ( SHANK3 ) gene, encoding excitatory postsynaptic core scaffolding proteins, are causally associated with numerous neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder, intellectual disability, and schizophrenia (SCZ). Although detailed synaptic changes of various Shank3 mutant mice have been well characterized, broader downstream molecular changes, including direct and indirect changes, remain largely unknown...
2018: Frontiers in Molecular Neuroscience
Androniki Raftogianni, Lena C Roth, Diego García-González, Thorsten Bus, Claudia Kühne, Hannah Monyer, Daniel J Spergel, Jan M Deussing, Valery Grinevich
Based on pharmacological studies, corticotropin-releasing hormone (CRH) and its receptors play a leading role in the inhibition of the hypothalamic-pituitary-gonadal (HPG) axis during acute stress. To further study the effects of CRH receptor signaling on the HPG axis, we generated and/or employed male mice lacking CRH receptor type 1 (CRHR1) or type 2 (CRHR2) in gonadotropin-releasing hormone neurons, GABAergic neurons, or in all central neurons and glia. The deletion of CRHRs revealed a preserved decrease of plasma luteinizing hormone (LH) in response to either psychophysical or immunological stress...
2018: Frontiers in Molecular Neuroscience
Andreas Strehl, Christos Galanis, Tijana Radic, Stephan Wolfgang Schwarzacher, Thomas Deller, Andreas Vlachos
Homeostatic plasticity mechanisms maintain neurons in a stable state. To what extent these mechanisms are relevant during the structural and functional maturation of neural tissue is poorly understood. To reveal developmental changes of a major homeostatic plasticity mechanism, i.e., homeostatic excitatory synaptic plasticity, we analyzed 1-week- and 4-week-old entorhino-hippocampal slice cultures and investigated the ability of immature and mature dentate granule cells (GCs) to express this form of plasticity...
2018: Frontiers in Molecular Neuroscience
Haitao Wang, Jiangping Xu, Philip Lazarovici, Remi Quirion, Wenhua Zheng
Dopamine is a brain neurotransmitter involved in the pathology of schizophrenia. The dopamine hypothesis states that, in schizophrenia, dopaminergic signal transduction is hyperactive. The cAMP-response element binding protein (CREB) is an intracellular protein that regulates the expression of genes that are important in dopaminergic neurons. Dopamine affects the phosphorylation of CREB via G protein-coupled receptors. Neurotrophins, such as brain derived growth factor (BDNF), are critical regulators during neurodevelopment and synaptic plasticity...
2018: Frontiers in Molecular Neuroscience
Md Jakaria, Shin-Young Park, Md Ezazul Haque, Govindarajan Karthivashan, In-Su Kim, Palanivel Ganesan, Dong-Kug Choi
Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In in vivo and in vitro models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs...
2018: Frontiers in Molecular Neuroscience
Catia Andreassi, Hamish Crerar, Antonella Riccio
Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their extraordinary cytoarchitecture. This formidable task is achieved, at least in part, by targeting mRNA to subcellular compartments where they are rapidly translated. mRNA transcripts are the conveyor of genetic information from DNA to the translational machinery, however, they are also endowed with additional functions linked to both the coding sequence (open reading frame, or ORF) and the flanking 5' and 3' untranslated regions (UTRs), that may harbor coding-independent functions...
2018: Frontiers in Molecular Neuroscience
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