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https://www.readbyqxmd.com/read/29342141/monitoring-t-cell-dendritic-cell-interactions-in-vivo-by-intercellular-enzymatic-labelling
#1
Giulia Pasqual, Aleksey Chudnovskiy, Jeroen M J Tas, Marianna Agudelo, Lawrence D Schweitzer, Ang Cui, Nir Hacohen, Gabriel D Victora
Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy, this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29337302/critical-roles-of-%C3%AE-ii-spectrin-in-brain-development-and-epileptic-encephalopathy
#2
Yu Wang, Tuo Ji, Andrew D Nelson, Katarzyna Glanowska, Geoffrey G Murphy, Paul M Jenkins, Jack M Parent
The nonerythrocytic α-spectrin-1 (SPTAN1) gene encodes the cytoskeletal protein αII spectrin. Mutations in SPTAN1 cause early infantile epileptic encephalopathy type 5 (EIEE5); however, the role of αII spectrin in neurodevelopment and EIEE5 pathogenesis is unknown. Prior work suggests that αII spectrin is absent in the axon initial segment (AIS) and contributes to a diffusion barrier in the distal axon. Here, we have shown that αII spectrin is expressed ubiquitously in rodent and human somatodendritic and axonal domains...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337116/impact-of-swiprosin-1-efhd2-on-adult-hippocampal-neurogenesis
#3
Martin Regensburger, Iryna Prots, Dorothea Reimer, Sebastian Brachs, Sandra Loskarn, Dieter Chichung Lie, Dirk Mielenz, Beate Winner
Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and in the adult. EFHD2 is regulated by Ca2+ binding, stabilizes F-actin, and promotes neurite extension. Previous studies indicated a dysregulation of EFHD2 in human Alzheimer's disease brains. We hypothesized a detrimental effect of genetic ablation of Efhd2 on hippocampal integrity and specifically investigated adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal development and in mature neurons. We observed a severe reduction of the survival of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast stage...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29335431/synaptic-localisation-of-srf-coactivators-mkl1-and-mkl2-and-their-role-in-dendritic-spine-morphology
#4
Marisa Kaneda, Hiroyuki Sakagami, Yamato Hida, Toshihisa Ohtsuka, Natsumi Satou, Yuta Ishibashi, Mamoru Fukuchi, Anna Krysiak, Mitsuru Ishikawa, Daisuke Ihara, Katarzyna Kalita, Akiko Tabuchi
The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#5
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29330744/c-fos-downregulation-positively-regulates-epha5-expression-in-a-congenital-hypothyroidism-rat-model
#6
Honghua Song, Yuqin Zheng, Fuying Cai, Yanyan Ma, Jingyue Yang, Youjia Wu
The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29324888/transcription-factor-runx1-is-pro-neurogenic-in-adult-hippocampal-precursor-cells
#7
Hirokazu Fukui, Annette Rünker, Klaus Fabel, Frank Buchholz, Gerd Kempermann
Transcription factor Runx1 (Runt Related Transcription Factor 1), plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells...
2018: PloS One
https://www.readbyqxmd.com/read/29323797/relations-between-cortical-thickness-serotonin-1a-receptor-binding-and-structural-connectivity-a-multimodal-imaging-study
#8
Rajapillai L I Pillai, Ashwin Malhotra, Deborah D Rupert, Bennett Weschler, John C Williams, Mengru Zhang, Jie Yang, J John Mann, Maria A Oquendo, Ramin V Parsey, Christine DeLorenzo
Serotonin 1A (5-HT1A ) receptors play a direct role in neuronal development, cell proliferation, and dendritic branching. We hypothesized that variability in 5-HT1A binding can affect cortical thickness, and may account for a subtype of major depressive disorder (MDD) in which both are altered. To evaluate this, we measured cortical thickness from structural magnetic resonance imaging (MRI) and 5-HT1A binding by positron emission tomography (PET) in an exploratory study. To examine a range of 5-HT1A binding and cortical thickness values, we recruited 25 healthy controls and 19 patients with MDD...
February 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29323291/neurexin-controls-plasticity-of-a-mature-sexually-dimorphic-neuron
#9
Michael P Hart, Oliver Hobert
During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (γ-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29322238/development-of-inhibitory-synaptic-inputs-on-layer-2-3-pyramidal-neurons-in-the-rat-medial-prefrontal-cortex
#10
Mari A Virtanen, Claudia Marvine Lacoh, Hubert Fiumelli, Markus Kosel, Shiva Tyagarajan, Mathias de Roo, Laszlo Vutskits
Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons...
January 10, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29317193/an-essential-role-for-neuregulin-4-in-the-growth-and-elaboration-of-developing-neocortical-pyramidal-dendrites
#11
Blanca Paramo, Sean Wyatt, Alun M Davies
Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4-/- neonates in vivo compared with Nrg4+/+ littermates...
January 6, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29313800/kif2a-regulates-the-development-of-dentate-granule-cells-and-postnatal-hippocampal-wiring
#12
Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G Chaudhary, Mohammed H Al-Qahtani, Nobutaka Hirokawa
Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expressed in the hippocampus, in which new neurons are generated throughout an individual's life in established neuronal circuits. In this study, we investigated KIF2A function in the postnatal hippocampus by using tamoxifen-inducible Kif2a conditional knockout (Kif2a-cKO) mice...
January 9, 2018: ELife
https://www.readbyqxmd.com/read/29306053/cd38-is-required-for-dendritic-organisation-in-visual-cortex-and-hippocampus
#13
Thom P Nelissen, Rosemary A Bamford, Shiro Tochitani, Kamuran Akkus, Aurimas Kudzinskas, Kenichiro Yokoi, Hiroshi Okamoto, Yasuhiko Yamamoto, J Peter H Burbach, Hideo Matsuzaki, Asami Oguro-Ando
Morphological screening of mouse brains with known behavioural deficits can give great insight into the relationship between brain regions and their behaviour. Oxytocin- and CD38-deficient mice have previously been shown to have behavioural phenotypes, such as restrictions in social memory, social interactions, and maternal behaviour. CD38 is reported as an autism spectrum disorder (ASD) candidate gene and these behavioural phenotypes may be linked to ASD. To address whether these behavioural phenotypes relate to brain pathology and neuronal morphology, here we investigate the morphological changes in the CD38-deficient mice brains, with focus on the pathology and neuronal morphology of the cortex and hippocampus, using Nissl staining, immunohistochemistry, and Golgi staining...
January 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29305536/pou6f1-mediates-neuropeptide-dependent-plasticity-in-the-adult-brain
#14
Cynthia K McClard, Mikhail Y Kochukov, Isabella Herman, Zhandong Liu, Aiden Eblimit, Yalda Moayedi, Joshua Ortiz-Guzman, Daniel Colchado, Brandon Pekarek, Sugi Paneerselvam, Graeme Mardon, Benjamin R Arenkiel
The mouse olfactory bulb (OB) features continued, activity-dependent integration of adult-born neurons, providing a robust model to examine mechanisms of plasticity in the adult brain. We previously reported that local OB interneurons secrete the neuropeptide corticotropin releasing hormone (CRH) in an activity-dependent manner onto adult-born granule neurons, and that local CRH signaling promotes expression of synaptic machinery in the bulb. This effect is mediated via activation of the CRH receptor 1 (CRHR1), which is developmentally regulated during adult-born neuron maturation...
January 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29286375/inducing-cre-lox-recombination-in-mouse-cerebral-cortex-through-in-utero-electroporation
#15
Katherine M Bland, Zachary O Casey, Christopher J Handwerk, Z Logan Holley, George S Vidal
Cell-autonomous neuronal functions of genes can be revealed by causing loss or gain of function of a gene in a small and sparse population of neurons. To do so requires generating a mosaic in which neurons with loss or gain of function of a gene are surrounded by genetically unperturbed tissue. Here, we combine the Cre-lox recombination system with in utero electroporation in order to generate mosaic brain tissue that can be used to study the cell-autonomous function of genes in neurons. DNA constructs (available through repositories), coding for a fluorescent label and Cre recombinase, are introduced into developing cortical neurons containing genes flanked with loxP sites in the brains of mouse embryos using in utero electroporation...
November 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285893/cerebellar-microglia-are-dynamically-unique-and-survey-purkinje-neurons-in-vivo
#16
Rianne D Stowell, Elissa L Wong, Hanna N Batchelor, Monique S Mendes, Cassandra E Lamantia, Brendan S Whitelaw, Ania K Majewska
Microglia are the innate immune cells of the central nervous system and are also important participants in normal development and synaptic plasticity. Here we demonstrate that the microglia of the mouse cerebellum represent a unique population compared to cortical microglia. Microglia are more sparsely distributed within the cerebellum and have a markedly less ramified morphology compared to their cortical counterparts. Using time-lapse in vivo imaging, we found that these differences in distribution and morphology ultimately lead to decreased parenchymal surveillance by cerebellar microglia...
December 29, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29285738/developmental-changes-of-synaptic-and-extrasynaptic-nmda-receptor-expression-in-rat-cerebellar-neurons-in-vitro
#17
Dmitry A Sibarov, Yulia D Stepanenko, Ivan V Silantiev, Polina A Abushik, Tatiana V Karelina, Sergei M Antonov
Transient expression of different NMDA receptors (NMDARs) plays a role in development of the cerebellum. Whether similar processes undergo during neuronal differentiation in culture is not clearly understood. We studied NMDARs in cerebellar neurons in cultures of 7 and 21 days in vitro (DIV) using immunocytochemical and electrophysiological approaches. Whereas at 7 DIV, the vast majority of neurons were immunopositive for GluN2 subunits, further synaptoginesis was accompanied by the time-dependent loss of NMDARs...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29281813/loss-of-synapse-repressor-mdga1-enhances-perisomatic-inhibition-confers-resistance-to-network-excitation-and-impairs-cognitive-function
#18
Steven A Connor, Ina Ammendrup-Johnsen, Yasushi Kishimoto, Parisa Karimi Tari, Vedrana Cvetkovska, Takashi Harada, Daiki Ojima, Tohru Yamamoto, Yu Tian Wang, Ann Marie Craig
Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29276004/missense-variants-in-rhobtb2-cause-a-developmental-and-epileptic-encephalopathy-in-humans-and-altered-levels-cause-neurological-defects-in-drosophila
#19
Jonas Straub, Enrico D H Konrad, Johanna Grüner, Annick Toutain, Levinus A Bok, Megan T Cho, Heather P Crawford, Holly Dubbs, Ganka Douglas, Rebekah Jobling, Diana Johnson, Bryan Krock, Mohamad A Mikati, Addie Nesbitt, Joost Nicolai, Meredith Phillips, Annapurna Poduri, Xilma R Ortiz-Gonzalez, Zöe Powis, Avni Santani, Lacey Smith, Alexander P A Stegmann, Constance Stumpel, Maaike Vreeburg, Anna Fliedner, Anne Gregor, Heinrich Sticht, Christiane Zweier
Although the role of typical Rho GTPases and other Rho-linked proteins in synaptic plasticity and cognitive function and dysfunction is widely acknowledged, the role of atypical Rho GTPases (such as RHOBTB2) in neurodevelopment has barely been characterized. We have now identified de novo missense variants clustering in the BTB-domain-encoding region of RHOBTB2 in ten individuals with a similar phenotype, including early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorders...
December 13, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29274743/ankrd11-associated-with-intellectual-disability-and-autism-regulates-dendrite-differentiation-via-the-bdnf-trkb-signaling-pathway
#20
Minhan Ka, Woo-Yang Kim
Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing moue cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons...
December 21, 2017: Neurobiology of Disease
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