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https://www.readbyqxmd.com/read/29300891/loss-of-cntnap2-causes-axonal-excitability-deficits-developmental-delay-in-cortical-myelination-and-abnormal-stereotyped-motor-behavior
#1
Ricardo Scott, Alberto Sánchez-Aguilera, Kim van Elst, Lynette Lim, Nathalie Dehorter, Sung Eun Bae, Giorgia Bartolini, Elior Peles, Martien J H Kas, Hilgo Bruining, Oscar Marín
Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons...
December 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29297312/generation-of-megabase-scale-deletions-inversions-and-duplications-involving-the-contactin-6-gene-in-mice-by-crispr-cas9-technology
#2
Alexei N Korablev, Irina A Serova, Oleg L Serov
BACKGROUND: Copy Number Variation (CNV) of the human CNTN6 gene (encoding the contactin-6 protein), caused by deletions or duplications, is responsible for severe neurodevelopmental impairments, often in combination with facial dysmorphias. Conversely, deleterious point mutations of this gene do not show any clinical phenotypes. The aim of this study is to generate mice carrying large deletions, duplications and inversions involving the Cntn6 gene as a new experimental model to study CNV of the human CNTN6 locus...
December 28, 2017: BMC Genetics
https://www.readbyqxmd.com/read/29244234/mechanisms-of-caspr2-antibodies-in-autoimmune-encephalitis-and-neuromyotonia
#3
Kristina R Patterson, Josep Dalmau, Eric Lancaster
OBJECTIVE: To determine the pathogenic mechanisms of autoantibodies to the cell adhesion molecule Caspr2 in acquired neuromyotonia and autoimmune encephalitis. METHODS: Caspr2 positive samples were confirmed using a cell-based assay, and their IgG subtypes were determined by ELISA and cell-based assay. A solid phase binding assay quantified the binding of Caspr2 to contactin-2 in the presence of Caspr2 autoantibodies. Living cultures of primary rat hippocampal neurons were incubated with Caspr2-positive or control sera and the distribution of Caspr2-positive immunofluorescent puncta and total surface Caspr2 were quantified...
December 15, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29238462/mechanisms-of-spinal-cord-injury-regeneration-in-zebrafish-a-systematic-review
#4
REVIEW
Zeynab Noorimotlagh, Mahla Babaie, Mahdi Safdarian, Tahereh Ghadiri, Vafa Rahimi-Movaghar
Objectives: To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. Materials and Methods: Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software. Results: Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29165835/the-function-of-contactin-2-tag-1-in-oligodendrocytes-in-health-and-demyelinating-pathology
#5
Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos
The oligodendrocyte maturation process and the transition from the pre-myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG-1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its involvement on oligodendrocyte maturation, branching, myelin-gene expression, myelination, and axonal function...
November 22, 2017: Glia
https://www.readbyqxmd.com/read/29090003/structure-and-function-of-the-contactin-associated-protein-family-in-myelinated-axons-and-their-relationship-with-nerve-diseases
#6
REVIEW
Yan Zou, Wei-Feng Zhang, Hai-Ying Liu, Xia Li, Xing Zhang, Xiao-Fang Ma, Yang Sun, Shi-Yi Jiang, Quan-Hong Ma, De-En Xu
The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family-CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29089585/antibodies-against-peripheral-nerve-antigens-in-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#7
Luis Querol, Ana M Siles, Roser Alba-Rovira, Agustín Jáuregui, Jérôme Devaux, Catherine Faivre-Sarrailh, Josefa Araque, Ricard Rojas-Garcia, Jordi Diaz-Manera, Elena Cortés-Vicente, Gisela Nogales-Gadea, Miquel Navas-Madroñal, Eduard Gallardo, Isabel Illa
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and one (1.5%) against the contactin-1/contactin-associated protein-1 complex...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29075658/improving-the-antibody-based-evaluation-of-autoimmune-encephalitis
#8
Lindsey McCracken, Junxian Zhang, Maxwell Greene, Anne Crivaro, Joyce Gonzalez, Malek Kamoun, Eric Lancaster
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65)...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29055902/lgi1-caspr2-and-related-antibodies-a-molecular-evolution-of-the-phenotypes
#9
REVIEW
Sophie N M Binks, Christopher J Klein, Patrick Waters, Sean J Pittock, Sarosh R Irani
Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity...
October 21, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28968899/cntnap4-impacts-epilepsy-through-gabaa-receptors-regulation-evidence-from-temporal-lobe-epilepsy-patients-and-mouse-models
#10
Yafei Shangguan, Xin Xu, Baigalimaa Ganbat, Yun Li, Wei Wang, Yong Yang, Xi Lu, Chao Du, Xin Tian, Xuefeng Wang
Epilepsy is a serious neurological condition characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Here, we demonstrated that the expression of contactin-associated protein-like 4 (CNTNAP4) was decreased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. Lentivirus-mediated knock-down of CNTNAP4 in the hippocampus increased mice susceptibility to epilepsy. Conversely, lentivirus-mediated overexpression of CNTNAP4 decreased epileptic behavior in mice...
August 22, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28966979/developmental-disruption-of-gabaar-meditated-inhibition-in-cntnap2-ko-mice
#11
Morgan S Bridi, Su Mi Park, Shiyong Huang
GABA released from presynaptic sites induces short-lived phasic inhibition mediated by synaptic GABAA receptors (GABAARs) and longer-duration tonic inhibition mediated by extrasynaptic GABAA or GABAB receptors (GABABRs). A number of studies have found that contactin-associated protein 2 (Cntnap2) knockout (KO) mice, a well-established mouse model of autism, exhibit reduced interneuron numbers and aberrant phasic inhibition. However, little is known about whether tonic inhibition is disrupted in Cntnap2 KO mice and when the disruption of inhibition begins to occur during postnatal development...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28947766/neurons-define-non-myelinated-axon-segments-by-the-regulation-of-galectin-4-containing-axon-membrane-domains
#12
Natalia Díez-Revuelta, Alonso M Higuero, Silvia Velasco, María Peñas-de-la-Iglesia, Hans-Joachim Gabius, José Abad-Rodríguez
The mechanism underlying selective myelination of axons versus dendrites or neuronal somata relies on the expression of somatodendritic membrane myelination inhibitors (i.e. JAM2). However, axons still present long unmyelinated segments proposed to contribute to axonal plasticity and higher order brain functions. Why these segments remain unmyelinated is still an unresolved issue. The bifunctional lectin galectin-4 (Gal-4) organizes the transport of axon glycoproteins by binding to N-acetyllactosamine (LacNac) termini of N-glycans...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28941200/decreased-neuro-axonal-proteins-in-csf-at-first-attack-of-suspected-multiple-sclerosis
#13
Marcel P Stoop, Tessel F Runia, Christoph Stingl, Roos M van der Vuurst de Vries, Theo M Luider, Rogier Q Hintzen
The pathology of multiple sclerosis is located in the central nervous system, therefore cerebrospinal fluid (CSF) is an attractive biofluid for biomarker research for proteins related to the early stages of this disease. In this study, the CSF proteome of patients with a clinically isolated syndrome of demyelination (CIS, a first attack of multiple sclerosis) is compared to the CSF proteome of control patients to identify differentially abundant proteins. CSF samples of 47 CIS patients and 45 control subjects are enzymatically digested and subsequently measured by LC-MS/MS (LTQ-Orbitrap)...
September 20, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28938490/expression-of-contactin-4-is-associated-with-malignant-behavior-in-pheochromocytomas-and-paragangliomas
#14
Lucie Evenepoel, Francien H van Nederveen, Lindsey Oudijk, Thomas G Papathomas, David F Restuccia, Eric J T Belt, Wouter W de Herder, Richard A Feelders, Gaston J H Franssen, Marc Hamoir, Dominique Maiter, Aurel Perren, Henri J L M Timmers, Susanne van Eeden, Laurent Vroonen, Selda Aydin, Mercedes Robledo, Miikka Vikkula, Ronald R de Krijger, Winand N M Dinjens, Alexandre Persu, Esther Korpershoek
Context: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine, usually benign tumors. Currently, the only reliable criterion of malignancy is the presence of metastases. Objective: The aim was to identify genes associated with malignancy in PPGL. Design: Transcriptomic profiling was performed on 40 benign and 11 malignant PPGL. Genes showing a significantly different expression between benign and malignant PPGL with a ratio ≥ 4 were confirmed, and subsequently tested in an independent series by qRT-PCR...
August 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28934754/cntn-1-enhances-chemoresistance-in-human-lung-adenocarcinoma-through-induction-of-epithelial-mesenchymal-transition-by-targeting-the-pi3k-akt-pathway
#15
Ruijie Zhang, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, Wenxiang Tang, Yan Zhou, Jianping Xu, Pei Li
BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28920570/brain-relevant-antibodies-in-first-episode-psychosis-a-matched-case-control-study
#16
Fiona Gaughran, John Lally, Katherine Beck, Ruaidhri McCormack, Poonam Gardner-Sood, Ester Coutinho, Leslie Jacobson, Bethan Lang, Ricardo Sainz-Fuertes, Evangelos Papanastasiou, Marta Di Forti, Tim Nicholson, Angela Vincent, Robin M Murray
BACKGROUND: There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP). METHODS: Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study...
September 18, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28901288/multiple-conserved-cell-adhesion-protein-interactions-mediate-neural-wiring-of-a-sensory-circuit-in-c-elegans
#17
Byunghyuk Kim, Scott W Emmons
Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG...
September 13, 2017: ELife
https://www.readbyqxmd.com/read/28861035/molecular-disorganization-of-axons-adjacent-to-human-cortical-microinfarcts
#18
Hamza Coban, Spencer Tung, Bryan Yoo, Harry V Vinters, Jason D Hinman
Cortical microinfarcts (CMIs) are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer's disease as well as other forms of dementia...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28860054/detection-of-contactin-2-in-cerebrospinal-fluid-csf-of-patients-with-alzheimer-s-disease-using-fluorescence-correlation-spectroscopy-fcs
#19
Madhurima Chatterjee, Bernd Nöding, Eline A J Willemse, Marleen J A Koel-Simmelink, Wiesje M van der Flier, Detlev Schild, Charlotte E Teunissen
OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in the world. As many AD biomarkers occur at rather low abundances in CSF or blood, techniques of very high sensitivity and accuracy are important as diagnostic tools in the clinic. Here, we aimed to provide proof of concept of the use of a single molecule detection technique, Fluorescence Correlation Spectroscopy (FCS) for detection of novel candidate biomarkers for AD. DESIGN AND METHODS: FCS detects the diffusion times of the antigen-antibody complexes in highly diluted sample solutions, thus eliminating the need of large sample volumes and allows estimating the concentration of the target antigen...
August 28, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28821864/nanomechanics-of-multidomain-neuronal-cell-adhesion-protein-contactin-revealed-by-single-molecule-afm-and-smd
#20
K Mikulska-Ruminska, A J Kulik, C Benadiba, I Bahar, G Dietler, W Nowak
Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations...
August 18, 2017: Scientific Reports
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