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Frontiers in Molecular Neuroscience

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[This corrects the article on p. 143 in vol. 9, PMID: 28018171.].
2017: Frontiers in Molecular Neuroscience
Christoph Becker-Pauly, Claus U Pietrzik
The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments...
2016: Frontiers in Molecular Neuroscience
Soomin Kim, Kelly Tellez, Graham Buchan, Tim Lebestky
Optomotor behavior represents a stereotyped locomotor response to visual motion that is found in both vertebrate and invertebrate models. The Fly Stampede assay was developed to study an optomotor response in freely walking populations of Drosophila. Here we share optimized assay designs and software for production of a modified stampede assay that can be used for genetic screens, and improved tracking outputs for understanding behavioral parameters of visual-motion responses and arousal state of individual animals...
2016: Frontiers in Molecular Neuroscience
Vera G Volpi, Thierry Touvier, Maurizio D'Antonio
Reaching the correct three-dimensional structure is crucial for the proper function of a protein. The endoplasmic reticulum (ER) is the organelle where secreted and transmembrane proteins are synthesized and folded. To guarantee high fidelity of protein synthesis and maturation in the ER, cells have evolved ER-protein quality control (ERQC) systems, which assist protein folding and promptly degrade aberrant gene products. Only correctly folded proteins that pass ERQC checkpoints are allowed to exit the ER and reach their final destination...
2016: Frontiers in Molecular Neuroscience
Carlo Rinaldi, Imre Mäger, Matthew J Wood
The accumulation in neurons of aberrant protein species, the pathological hallmark of many neurodegenerative diseases, results from a global impairment of key cellular processes governing protein synthesis/degradation and repair mechanisms, also known as the proteostasis network (PN). The growing number of connections between dysfunction of this intricate network of pathways and diseases of the motor unit, where both motor neurons and muscle are primarily affected, has provided momentum to investigate the muscle- and motor neuron-specific response to physiological and pathological stressors and to explore the therapeutic opportunities that manipulation of this process may offer...
2016: Frontiers in Molecular Neuroscience
Maria-Letizia Campanari, María-Salud García-Ayllón, Sorana Ciura, Javier Sáez-Valero, Edor Kabashi
Amyotrophic Lateral Sclerosis (ALS) is a highly debilitating disease caused by progressive degeneration of motorneurons (MNs). Due to the wide variety of genes and mutations identified in ALS, a highly varied etiology could ultimately converge to produce similar clinical symptoms. A major hypothesis in ALS research is the "distal axonopathy" with pathological changes occurring at the neuromuscular junction (NMJ), at very early stages of the disease, prior to MNs degeneration and onset of clinical symptoms. The NMJ is a highly specialized cholinergic synapse, allowing signaling between muscle and nerve necessary for skeletal muscle function...
2016: Frontiers in Molecular Neuroscience
Ce Xie, Tomohiro Miyasaka
Dementia includes several diseases characterized by acquired and irreversible brain dysfunctions that interfere with daily life. According to the etiology, dementia can be induced by poisoning or metabolic disorders, and other cases of dementia have a clear pathogenesis. However, half of neurodegenerative diseases have an unclear pathogenesis and etiology. Alzheimer's disease (AD), Lewy body dementia and frontal-temporal dementia are the three most common types of dementia. These neurodegenerative diseases are characterized by the appearance of the following specific protein inclusions: amyloid beta and tau in AD; α-synuclein in Lewy body dementia; and tau, TDP-43, or FUS in frontal-temporal dementia...
2016: Frontiers in Molecular Neuroscience
Alice Pulga, Yves Porte, Jean-Luc Morel
Centrifugation is a widely used procedure to study the impact of altered gravity on Earth, as observed during spaceflights, allowing us to understand how a long-term physical constraint can condition the mammalian physiology. It is known that mice, placed in classical cages and maintained during 21 days in a centrifuge at 3G gravity level, undergo physiological adaptations due to hypergravity, and/or stress. Indeed, an increase of corticosterone levels has been previously measured in the plasma of 3G-exposed mice...
2016: Frontiers in Molecular Neuroscience
Yan He, Yan Li, Mozi Chen, Zhilan Pu, Feiyang Zhang, Long Chen, Yang Ruan, Xinran Pan, Chaoxiang He, Xingjun Chen, Zhihui Li, Jiang-Fan Chen
Striatal adenosine A2A receptors (A2ARs) modulate striatal synaptic plasticity and instrumental learning, possibly by functional interaction with the dopamine D2 receptors (D2Rs) and metabotropic glutamate receptors 5 (mGluR5) through receptor-receptor heterodimers, but in vivo evidence for these interactions is lacking. Using in situ proximity ligation assay (PLA), we studied the subregional distribution of the A2AR-D2R and A2AR-mGluR5 heterodimer complexes in the striatum and their adaptive changes over the random interval and random ratio training of instrumental learning...
2016: Frontiers in Molecular Neuroscience
Cédric Francius, María Hidalgo-Figueroa, Stéphanie Debrulle, Barbara Pelosi, Vincent Rucchin, Kara Ronellenfitch, Elena Panayiotou, Neoklis Makrides, Kamana Misra, Audrey Harris, Hessameh Hassani, Olivier Schakman, Carlos Parras, Mengqing Xiang, Stavros Malas, Robert L Chow, Frédéric Clotman
Spinal ventral interneurons regulate the activity of motor neurons, thereby controlling motor activities. Interneurons arise during embryonic development from distinct progenitor domains distributed orderly along the dorso-ventral axis of the neural tube. A single ventral progenitor population named p2 generates at least five V2 interneuron subsets. Whether the diversification of V2 precursors into multiple subsets occurs within the p2 progenitor domain or involves a later compartment of early-born V2 interneurons remains unsolved...
2016: Frontiers in Molecular Neuroscience
Gessica Sala, Daniele Marinig, Alessandro Arosio, Carlo Ferrarese
Chaperone-mediated autophagy (CMA) represents a selective form of autophagy involved in the degradation of specific soluble proteins containing a pentapeptide motif that is recognized by a cytosolic chaperone able to deliver proteins to the lysosomes for degradation. Physiologically, CMA contributes to maintain crucial cellular functions including energetic balance and protein quality control. Dysfunctions in CMA have been associated to the pathogenesis of several neurodegenerative diseases characterized by accumulation and aggregation of proteins identified as CMA substrates...
2016: Frontiers in Molecular Neuroscience
Mumtaz Kasim, Vicky Heß, Holger Scholz, Pontus B Persson, Michael Fähling
Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. Human achaete-scute homolog 1 (hASH1) is a proneural basic helix-loop-helix transcription factor essential for neurogenesis and is often upregulated in neuroblastoma. Here, we identified a novel function for hASH1 in regulating the differentiation phenotype of neuroblastoma cells...
2016: Frontiers in Molecular Neuroscience
Sonoko Hasegawa, Makiko Kumagai, Mitsue Hagihara, Hiroshi Nishimaru, Keizo Hirano, Ryosuke Kaneko, Atsushi Okayama, Teruyoshi Hirayama, Makoto Sanbo, Masumi Hirabayashi, Masahiko Watanabe, Takahiro Hirabayashi, Takeshi Yagi
The clustered protocadherin (Pcdh) genes are divided into the Pcdhα, Pcdhβ, and Pcdhγ clusters. Gene-disruption analyses in mice have revealed the in vivo functions of the Pcdhα and Pcdhγ clusters. However, all Pcdh protein isoforms form combinatorial cis-hetero dimers and enter trans-homophilic interactions. Here we addressed distinct and cooperative functions in the Pcdh clusters by generating six cluster-deletion mutants (Δα, Δβ, Δγ, Δαβ, Δβγ, and Δαβγ) and comparing their phenotypes: Δα, Δβ, and Δαβ mutants were viable and fertile; Δγ mutants lived less than 12 h; and Δβγ and Δαβγ mutants died shortly after birth...
2016: Frontiers in Molecular Neuroscience
Junjie Liang, Ning Li, Yanli Zhang, Changyi Hou, Xiaohan Yang, Takahiro Shimizu, Xiaoyu Wang, Kazuhiro Ikenaka, Kai Fan, Jianmei Ma
Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors...
2016: Frontiers in Molecular Neuroscience
Emanuel Lauber, Federica Filice, Beat Schwaller
Autism spectrum disorders (ASD) comprise a number of heterogeneous neurodevelopmental diseases characterized by core behavioral symptoms in the domains of social interaction, language/communication and repetitive or stereotyped patterns of behavior. In utero exposure to valproic acid (VPA) has evolved as a highly recognized rodent ASD model due to the robust behavioral phenotype observed in the offspring and the proven construct-, face- and predictive validity of the model. The number of parvalbumin-immunoreactive (PV(+)) GABAergic interneurons has been consistently reported to be decreased in human ASD subjects and in ASD animal models...
2016: Frontiers in Molecular Neuroscience
Lisa Seipold, Paul Saftig
Tetraspanins are a family of ubiquitously expressed and conserved proteins, which are characterized by four transmembrane domains and the formation of a short and a large extracellular loop (LEL). Through interaction with other tetraspanins and transmembrane proteins such as growth factors, receptors and integrins, tetraspanins build a wide ranging and membrane spanning protein network. Such tetraspanin-enriched microdomains (TEMs) contribute to the formation and stability of functional signaling complexes involved in cell activation, adhesion, motility, differentiation, and malignancy...
2016: Frontiers in Molecular Neuroscience
Fanny S Ng, Sukanya Sengupta, Yanmei Huang, Amy M Yu, Samantha You, Mary A Roberts, Lakshmanan K Iyer, Yongjie Yang, F Rob Jackson
Although, glial cells have well characterized functions in the developing and mature brain, it is only in the past decade that roles for these cells in behavior and plasticity have been delineated. Glial astrocytes and glia-neuron signaling, for example, are now known to have important modulatory functions in sleep, circadian behavior, memory and plasticity. To better understand mechanisms of glia-neuron signaling in the context of behavior, we have conducted cell-specific, genome-wide expression profiling of adult Drosophila astrocyte-like brain cells and performed RNA interference (RNAi)-based genetic screens to identify glial factors that regulate behavior...
2016: Frontiers in Molecular Neuroscience
Madeline L Pfau, Immanuel Purushothaman, Jian Feng, Sam A Golden, Hossein Aleyasin, Zachary S Lorsch, Hannah M Cates, Meghan E Flanigan, Caroline Menard, Mitra Heshmati, Zichen Wang, Avi Ma'ayan, Li Shen, Georgia E Hodes, Scott J Russo
Adult women are twice as likely as men to suffer from affective and anxiety disorders, although the mechanisms underlying heightened female stress susceptibility are incompletely understood. Recent findings in mouse Nucleus Accumbens (NAc) suggest a role for DNA methylation-driven sex differences in genome-wide transcriptional profiles. However, the role of another epigenetic process-microRNA (miR) regulation-has yet to be explored. We exposed male and female mice to Subchronic Variable Stress (SCVS), a stress paradigm that produces depression-like behavior in female, but not male, mice, and performed next generation mRNA and miR sequencing on NAc tissue...
2016: Frontiers in Molecular Neuroscience
Yang Lu, Shan Lei, Ning Wang, Pan Lu, Weisong Li, Juan Zheng, Praveen K Giri, Haixia Lu, Xinlin Chen, Zhiyi Zuo, Yong Liu, Pengbo Zhang
It has been suggested that ketamine cause injury during developing brain. Minocycline (MC) could prevent neuronal cell death through the activation of cell survival signals and the inhibition of apoptotic signals in models of neurodegenerative diseases. Here we investigated the protective effect of MC against ketamine-induced injury in neural stem cells (NSCs) from neonatal rat. Ketamine (100 μM/L) significantly inhibited NSC proliferation, promoted their differentiation into astrocytes and suppressed neuronal differentiation of NSCs...
2016: Frontiers in Molecular Neuroscience
Cara J Westmark, Shih-Chieh Chuang, Seth A Hays, Mikolaj J Filon, Brian C Ray, Pamela R Westmark, Jay R Gibson, Kimberly M Huber, Robert K S Wong
Amyloid-beta protein precursor (APP) and metabolite levels are altered in fragile X syndrome (FXS) patients and in the mouse model of the disorder, Fmr1(KO) mice. Normalization of APP levels in Fmr1(KO) mice (Fmr1(KO) /APP(HET) mice) rescues many disease phenotypes. Thus, APP is a potential biomarker as well as therapeutic target for FXS. Hyperexcitability is a key phenotype of FXS. Herein, we determine the effects of APP levels on hyperexcitability in Fmr1(KO) brain slices. Fmr1(KO) /APP(HET) slices exhibit complete rescue of UP states in a neocortical hyperexcitability model and reduced duration of ictal discharges in a CA3 hippocampal model...
2016: Frontiers in Molecular Neuroscience
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