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https://www.readbyqxmd.com/read/28544974/cetuximab-modified-collagen-scaffold-directs-neurogenesis-of-injury-activated-endogenous-neural-stem-cells-for-acute-spinal-cord-injury-repair
#1
Xing Li, Yannan Zhao, Shixiang Cheng, Sufang Han, Muya Shu, Bing Chen, Xuyi Chen, Fengwu Tang, Nuo Wang, Yue Tu, Bin Wang, Zhifeng Xiao, Sai Zhang, Jianwu Dai
Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28542195/differential-excitatory-control-of-2-parallel-basket-cell-networks-in-amygdala-microcircuits
#2
Tibor Andrási, Judit M Veres, Laura Rovira-Esteban, Richárd Kozma, Attila Vikór, Erzsébet Gregori, Norbert Hájos
Information processing in neural networks depends on the connectivity among excitatory and inhibitory neurons. The presence of parallel, distinctly controlled local circuits within a cortical network may ensure an effective and dynamic regulation of microcircuit function. By applying a combination of optogenetics, electrophysiological recordings, and high resolution microscopic techniques, we uncovered the organizing principles of synaptic communication between principal neurons and basket cells in the basal nucleus of the amygdala...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28539872/the-role-of-app-in-structural-spine-plasticity
#3
REVIEW
Elena Montagna, Mario M Dorostkar, Jochen Herms
Amyloid precursor protein (APP) is a transmembrane protein highly expressed in neurons. The full-length protein has cell-adhesion and receptor-like properties, which play roles in synapse formation and stability. Furthermore, APP can be cleaved by several proteases into numerous fragments, many of which affect synaptic function and stability. This review article focuses on the mechanisms of APP in structural spine plasticity, which encompasses the morphological alterations at excitatory synapses. These occur as changes in the number and morphology of dendritic spines, which correspond to the postsynaptic compartment of excitatory synapses...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28533206/myostatin-like-proteins-regulate-synaptic-function-and-neuronal-morphology
#4
Hrvoje Augustin, Kieran McGourty, Joern R Steinert, Helena M Cochemé, Jennifer Adcott, Melissa Cabecinha, Alec Vincent, Els F Halff, Josef T Kittler, Emmanuel Boucrot, Linda Partridge
Growth factors of the TGF-β superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of both Myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of Myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner...
May 22, 2017: Development
https://www.readbyqxmd.com/read/28530549/a-genetic-basis-for-molecular-asymmetry-at-vertebrate-electrical-synapses
#5
Adam C Miller, Alex C Whitebirch, Arish N Shah, Kurt C Marsden, Michael Granato, John O'Brien, Cecilia B Moens
Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function...
May 22, 2017: ELife
https://www.readbyqxmd.com/read/28528963/neuronal-activity-patterns-in-the-developing-barrel-cortex
#6
Heiko J Luhmann, Rustem Khazipov
The developing barrel cortex reveals a rich repertoire of neuronal activity patterns, which have been also found in other sensory neocortical areas and in other species including the somatosensory cortex of preterm human infants. The earliest stage is characterized by asynchronous, sparse single cell firing at low frequencies. During the second stage neurons show correlated firing, which is initially mediated by electrical synapses and subsequently transforms into network bursts depending on chemical synapses...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527111/human-placenta-derived-mesenchymal-stem-cells-loaded-on-linear-ordered-collagen-scaffold-improves-functional-recovery-after-completely-transected-spinal-cord-injury-in-canine
#7
Sufang Han, Zhifeng Xiao, Xing Li, Huan Zhao, Bin Wang, Zhixue Qiu, Zhi Li, Xin Mei, Bai Xu, Caixia Fan, Bing Chen, Jin Han, Yanzheng Gu, Huilin Yang, Qin Shi, Jianwu Dai
Traumatic spinal cord injury (SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold (LOCS) and human placenta-derived mesenchymal stem cells (hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment (control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans (CSPGs) expression...
May 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28524815/anchoring-high-concentrations-of-syngap-at-postsynaptic-densities-via-liquid-liquid-phase-separation
#8
Menglong Zeng, Guanhua Bai, Mingjie Zhang
SynGAP, encoded by SYNGAP1, is a Ras/Rap GTPase activator specifically expressed in the nervous systems. SynGAP is one of the most abundant proteins in the postsynaptic densities (PSDs) of excitatory synapses and acts as a critical synaptic activity brake by tuning down synaptic GTPase activities. Mutations of SYNGAP1 have been frequently linked to brain disorders including intellectual disability, autisms, and seizure. SynGAP has been shown to undergo fast dispersions from synapses in response to stimulations, a strategy that neurons use to control the specific activities of the enzyme within the tiny, semi-open compartments in dendritic spines...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28521702/role-of-ectonucleotidases-in-the-synapse-formation-during-brain-development-physiological-and-pathological-implications
#9
Ivana Grković, Dunja Drakulić, Jelena Martinović, Nataša Mitrović
Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eN)...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28502042/tale-of-the-good-and-the-bad-cdk5-remodeling-of-the-actin-cytoskeleton-in-the-brain
#10
REVIEW
Kavita Shah, Sandra Rossie
Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28500132/the-zinc-finger-e-box-binding-homeobox-1-zeb1-promotes-the-conversion-of-mouse-fibroblasts-into-functional-neurons
#11
Long Yan, Yue Li, Zixiao Shi, Xiaoyin Lu, Jiao Ma, Baoyang Hu, Jianwei Jiao, Hongmei Wang
The zinc finger E-box binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition (EMT). Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond EMT remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors Achaete-scute family bHLH transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2) and Neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28497586/r-ras-deficiency-does-not-affect-papain-induced-ige-production-in-mice
#12
Laura Kummola, Zsuzsanna Ortutay, Maria Vähätupa, Stuart Prince, Hannele Uusitalo-Järvinen, Tero A H Järvinen, Ilkka S Junttila
INTRODUCTION: R-Ras GTPase has recently been implicated in the regulation of immune functions, particularly in dendritic cell (DC) maturation, immune synapse formation, and subsequent T cell responses. METHODS: Here, we investigated the role of R-Ras in allergen-induced immune response (type 2 immune response) in Rras deficient (R-Ras KO) and wild type (WT) mice. RESULTS: Initially, we found that the number of conventional DC's in the lymph nodes (LNs) was reduced in R-Ras KO mice...
May 11, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28496137/tumor-suppressor-menin-is-required-for-subunit-specific-nachr-%C3%AE-5-transcription-and-nachr-dependent-presynaptic-facilitation-in-cultured-mouse-hippocampal-neurons
#13
Angela M Getz, Fenglian Xu, Frank Visser, Roger Persson, Naweed I Syed
In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495800/mechanically-patterned-neuromuscular-junctions-in-a-dish-have-improved-functional-maturation
#14
Cassandra L Happe, Kevin P Tenerelli, Anastasia K Gromova, Frederic Kolb, Adam J Engler
Motor neuron (MN) diseases are progressive disorders resulting from degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle fibers. NMJ-in-a-dish models have been developed to examine human MN-associated dysfunction with disease; however such co-culture models have randomly oriented myotubes with immature synapses that contract asynchronously. Mechanically patterned (MP) extracellular matrix with alternating soft and stiff stripes improve current NMJ-in-a-dish models by inducing both mouse and human myoblast durotaxis to stripes where they aligned, differentiated, and fused into patterned myotubes...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28494216/cough-reflex-hypersensitivity-a-role-for-neurotrophins
#15
Ahmed Z El-Hashim, Sahar M Jaffal
Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs)...
March 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28494186/small-interference-itga6-gene-targeting-in-the-human-thymic-epithelium-differentially-regulates-the-expression-of-immunological-synapse-related-genes
#16
Daiane Cristina F Golbert, Eliane Santana-Van-Vliet, Marcelo Ribeiro-Alves, Marbella Maria B da Fonsêca, Ailin Lepletier, Daniella Arêas Mendes-da-Cruz, Guilherme Loss, Vinícius Cotta-de-Almeida, Ana Tereza R Vasconcelos, Wilson Savino
The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ...
May 11, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28493559/mtor-referees-memory-and-disease-through-mrna-repression-and-competition
#17
REVIEW
Kimberly F Raab-Graham, Farr Niere
Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesized that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders...
May 11, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28493018/emerging-role-of-mirna-in-attention-deficit-hyperactivity-disorder-a-systematic-review
#18
REVIEW
Saurabh Srivastav, Susanne Walitza, Edna Grünblatt
Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder whose aetiology still remains elusive. Nevertheless, evidence supports a high genetic contribution that interacts with environmental factors, also known to modulate epigenetic processes. These epigenetic modulators are a class of non-coding RNAs, microRNAs (miRNAs), known as post-transcriptional regulators, which have emerged as prospective players in neuropsychiatric disorders since they play a role in brain development, synapse formation, and the fine-tuning of genes underlying synaptic and memory formation...
May 10, 2017: Attention Deficit and Hyperactivity Disorders
https://www.readbyqxmd.com/read/28490756/expressing-acetylcholine-receptors-after-innervation-suppresses-spontaneous-vesicle-release-and-causes-muscle-fatigue
#19
Meghan Mott, Victor M Luna, Jee-Young Park, Gerald B Downes, Kimberly Epley, Fumihito Ono
The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490573/dok7-gene-therapy-enhances-motor-activity-and-life-span-in-als-model-mice
#20
Sadanori Miyoshi, Tohru Tezuka, Sumimasa Arimura, Taro Tomono, Takashi Okada, Yuji Yamanashi
Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor neurodegenerative disease with severe muscle atrophy. The glutamate release inhibitor riluzole is the only medication approved by the FDA, and prolongs patient life span by a few months, testifying to a strong need for new treatment strategies. In ALS, motor neuron degeneration first becomes evident at the motor nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse between motor neuron and skeletal muscle; degeneration then progresses proximally, implicating the NMJ as a therapeutic target...
May 10, 2017: EMBO Molecular Medicine
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