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https://www.readbyqxmd.com/read/29053192/dissociation-of-nnos-from-psd-95-promotes-functional-recovery-after-cerebral-ischaemia-in-mice-through-reducing-excessive-tonic-gaba-release-from-reactive-astrocytes
#1
Yu-Hui Lin, Hai-Ying Liang, Ke Xu, Huan-Yu Ni, Jian Dong, Hui Xiao, Lei Chang, Hai-Yin Wu, Fei Li, Dong-Ya Zhu, Chun-Xia Luo
Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein Tat-nNOS-N1-133 or systemic administration of a small molecule ZL006 from days 4 to 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome...
October 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29051843/alterations-in-micro-rna-messenger-rna-mirna-mrna-coupled-signaling-networks-in-sporadic-alzheimer-s-disease-ad-hippocampal-ca1
#2
V Jaber, Y Zhao, W J Lukiw
RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and bioinformatics analysis have uncovered a small family of up-regulated human brain enriched microRNAs (miRNAs) and down-regulated messenger RNAs (mRNAs) in short post-mortem interval (PMI) sporadic Alzheimer's disease (AD) brain. At the mRNA level, a large majority of the expression of human brain genes found to be down-regulated in sporadic AD appears to be a consequence of an up-regulation of a specific group of NF-kB-inducible microRNAs (miRNAs)...
April 2017: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/29031899/synapse-formation-in-the-brain-can-be-enhanced-by-co-administering-three-specific-nutrients
#3
Richard J Wurtman
The memory impairments of early Alzheimer's disease [AD] are thought to result from a deficiency in synapses within the hippocampus and related brain regions. This deficiency could result from an acceleration in synapse turnover - perhaps caused by an endogenous neurotoxin like A-beta oligomers - or from a decrease in the production of the synaptic membrane needed to form new synapses. An AD-associated decrease in synaptogenesis almost certainly does occur, inasmuch as major decreases are also observed in the numbers of hippocampal dendritic spines, the immediate cytologic precursor of glutamatergic synapses...
October 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29030575/adolescent-ethanol-exposure-enhances-nmda-receptor-mediated-currents-in-hippocampal-neurons-reversal-by-gabapentin
#4
H S Swartzwelder, Maeng-Hee Park, Shawn Acheson
Adolescent intermittent ethanol (AIE) exposure compromises neural function into adulthood. We have reported that astrocyte-secreted thrombospondins, and their target neuronal receptors (α2δ-1) are upregulated in the hippocampus in adulthood after AIE, suggesting aberrant excitatory synaptogenesis and hyperexcitability in memory-related circuits. Gabapentin antagonizes the interaction of thrombospondins (TSPs) with the α2δ-1 receptor, and thus may reverse or ameliorate the effects of AIE on hippocampal function...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29029200/lateral-cerebellar-nucleus-stimulation-has-selective-effects-on-glutamatergic-and-gabaergic-perilesional-neurogenesis-after-cortical-ischemia-in-the-rodent-model
#5
Hugh H Chan, Jessica Cooperrider, Zhihong Chen, John T Gale, Kenneth B Baker, Connor A Wathen, Claire R Modic, Hyun-Joo Park, Andre G Machado
BACKGROUND: Chronic deep brain stimulation of the rodent lateral cerebellar nucleus (LCN) has been demonstrated to enhance motor recovery following cortical ischemia. This effect is concurrent with synaptogenesis and expression of long-term potentiation markers in the perilesional cerebral cortex. OBJECTIVE: To further investigate the cellular changes associated with chronic LCN stimulation in the ischemic rodent by examining neurogenesis along the cerebellothalamocortical pathway...
September 27, 2017: Neurosurgery
https://www.readbyqxmd.com/read/29028947/dlx1-and-dlx2-promote-interneuron-gaba-synthesis-synaptogenesis-and-dendritogenesis
#6
Ramon Pla, Amelia Stanco, MacKenzie A Howard, Anna N Rubin, Daniel Vogt, Niall Mortimer, Inma Cobos, Gregory Brian Potter, Susan Lindtner, James D Price, Alex S Nord, Axel Visel, Christoph E Schreiner, Scott C Baraban, David H Rowitch, John L R Rubenstein
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29021345/direct-evidence-of-aplp1-trans-interactions-in-cell-cell-adhesion-platforms-investigated-via-fluorescence-fluctuation-spectroscopy
#7
Valentin Dunsing, Magnus Mayer, Filip Liebsch, Gerhard Multhaup, Salvatore Chiantia
The Amyloid-precursor-like protein 1 (APLP1) is a type I transmembrane protein which plays a role in synaptic adhesion and synaptogenesis. Past investigations indicated that APLP1 is involved in the formation of protein-protein complexes that bridge the junctions between neighboring cells. Nevertheless, APLP1-APLP1 trans interactions have never been directly observed in higher eukaryotic cells. Here, we investigated APLP1 interactions and dynamics directly in living human embryonic kidney (HEK) cells, using fluorescence fluctuation spectroscopy techniques, namely cross-correlation scanning fluorescence correlation spectroscopy (sFCS) and Number&Brightness (N&B)...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29018333/cadherin-13-deficiency-increases-dorsal-raphe-5-ht-neuron-density-and-prefrontal-cortex-innervation-in-the-mouse-brain
#8
Andrea Forero, Olga Rivero, Sina Wäldchen, Hsing-Ping Ku, Dominik P Kiser, Yvonne Gärtner, Laura S Pennington, Jonas Waider, Patricia Gaspar, Charline Jansch, Frank Edenhofer, Thérèse J Resink, Robert Blum, Markus Sauer, Klaus-Peter Lesch
Background: During early prenatal stages of brain development, serotonin (5-HT)-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR), innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28975140/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#9
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28974044/magnetic-force-driven-graphene-patterns-to-direct-synaptogenesis-of-human-neuronal-cells
#10
Kyung-Joon Min, Tae-Hyung Kim, Jeong-Woo Choi
Precise control of axonal growth and synaptic junction formation are incredibly important to repair and/or to mimic human neuronal network. Here, we report a graphene oxide (GO)-based hybrid patterns that were proven to be excellent for guiding axonal growth and its consequent synapse formation of human neural cells. Unlike the previous method that utilized micro-contacting printing technique to generate GO patterns, here, GO-encapsulated magnetic nanoparticles were first synthesized and utilized as core materials wherein the external magnetic force facilitated the transfer of GO film to the desired substrate...
October 2, 2017: Materials
https://www.readbyqxmd.com/read/28970473/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#11
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
October 2, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28957797/resveratrol-enhances-neurite-outgrowth-and-synaptogenesis-via-sonic-hedgehog-signaling-following-oxygen-glucose-deprivation-reoxygenation-injury
#12
Fanren Tang, Shuang Guo, Hongyan Liao, Pingping Yu, Li Wang, Xiaosong Song, Jixiang Chen, Qin Yang
BACKGROUND/AIMS: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh) signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt)1, the present study examined whether this is mediated by Shh signaling. METHODS: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R)...
September 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28955242/shortened-spadin-analogs-display-better-trek-1-inhibition-in-vivo-stability-and-antidepressant-activity
#13
Alaeddine Djillani, Mariel Pietri, Sébastien Moreno, Catherine Heurteaux, Jean Mazella, Marc Borsotto
Depression is a devastating mental disorder that affects 20% of the population worldwide. Despite their proven efficacy, antidepressants present a delayed onset of action and serious adverse effects. Seven years ago, we described spadin (PE 12-28) as a promising endogenous peptide with antidepressant activity. Spadin specifically blocks the TREK-1 channel. Previously, we showed in vivo that, spadin activity disappeared beyond 7 h after administration. In order to improve in vivo spadin stability and bioavailability, we screened spadin analogs and derivatives...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28953973/macroglia-derived-thrombospondin-2-regulates-alterations-of-presynaptic-proteins-of-retinal-neurons-following-elevated-hydrostatic-pressure
#14
Shuchao Wang, Tu Hu, Zhen Wang, Na Li, Lihong Zhou, Lvshuang Liao, Mi Wang, Libin Liao, Hui Wang, Leping Zeng, Chunling Fan, Hongkang Zhou, Kun Xiong, Jufang Huang, Dan Chen
Many studies on retinal injury and repair following elevated intraocular pressure suggest that the survival ratio of retinal neurons has been improved by various measures. However, the visual function recovery is far lower than expected. The homeostasis of retinal synapses in the visual signal pathway is the key structural basis for the delivery of visual signals. Our previous studies found that complicated changes in the synaptic structure between retinal neurons occurred much earlier than obvious degeneration of retinal ganglion cells in rat retinae...
2017: PloS One
https://www.readbyqxmd.com/read/28951326/developmental-roles-of-the-spontaneous-depolarization-wave-in-synaptic-network-formation-in-the-embryonic-brainstem
#15
Yoko Momose-Sato, Katsushige Sato
One of the earliest activities expressed within the developing central nervous system is a widely propagating wave-like activity, which we referred to as the depolarization wave. Despite considerable consensus concerning the global features of the activity, its physiological role is yet to be clarified. The depolarization wave is expressed during a specific period of functional synaptogenesis, and this developmental profile has led to the hypothesis that the wave plays some roles in synaptic network organization...
September 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28939259/developmental-trajectories-of-macroanatomical-structures-in-common-marmoset-brain
#16
Fumiko Seki, Keigo Hikishima, Yuji Komaki, Junichi Hata, Akiko Uematsu, Norio Okahara, Masafumi Yamamoto, Haruka Shinohara, Erika Sasaki, Hideyuki Okano
Morphometry studies of human brain development have revealed characteristics of some growth patterns, such as gray matter (GM) and white matter (WM), but the features that make human neurodevelopment distinct from that in other species remain unclear. Studies of the common marmoset (Callithrix jacchus), a small New World primate, can provide insights into unique features such as cooperative behaviors complementary to those from comparative analyses using mouse and rhesus monkey. In the present study, we analyzed developmental patterns of GM, WM, and cortical regions with volume measurements using longitudinal sample (23 marmosets; 11 male, 12 female) between the ages of one and 30months...
September 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28938161/the-diverse-actions-of-astrocytes-during-synaptic-development
#17
REVIEW
Alexandra P Bosworth, Nicola J Allen
In the developing brain, cortical circuits are established through a complex process of synaptogenesis, maturation, and synaptic pruning. Astrocytes carry out diverse functions during each of these stages to facilitate the formation of complex networks. Recent work has begun to demonstrate that these heterogeneous roles during excitatory synaptic development are determined by the astrocyte population, brain region, and neuron type. This review will focus on current findings which highlight cell type specific mechanisms of excitatory synaptogenesis, as well as multiple mechanisms engaged by astrocytes to facilitate synaptic maturation and pruning...
September 19, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28937989/limited-synapse-overproduction-can-speed-development-but-sometimes-with-long-term-energy-and-discrimination-penalties
#18
Harang Ju, Costa M Colbert, William B Levy
Neural circuit development requires that synapses be formed between appropriate neurons. In addition, for a hierarchical network, successful development involves a sequencing of developmental events. It has been suggested that one mechanism that helps speed up development of proper connections is an early overproduction of synapses. Using a computational model of synapse development, such as adaptive synaptogenesis, it is possible to study such overproduction and its role in speeding up development; it is also possible to study other outcomes of synapse overproduction that are seemingly new to the literature...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28933765/potential-role-of-microtubule-stabilizing-agents-in-neurodevelopmental-disorders
#19
REVIEW
Sara Anna Bonini, Andrea Mastinu, Giulia Ferrari-Toninelli, Maurizio Memo
Neurodevelopmental disorders (NDDs) are characterized by neuroanatomical abnormalities indicative of corticogenesis disturbances. At the basis of NDDs cortical abnormalities, the principal developmental processes involved are cellular proliferation, migration and differentiation. NDDs are also considered "synaptic disorders" since accumulating evidence suggests that NDDs are developmental brain misconnection syndromes characterized by altered connectivity in local circuits and between brain regions. Microtubules and microtubule-associated proteins play a fundamental role in the regulation of basic neurodevelopmental processes, such as neuronal polarization and migration, neuronal branching and synaptogenesis...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28928363/an-autism-spectrum-disorder-related-de-novo-mutation-hotspot-discovered-in-the-gef1-domain-of-trio
#20
Anastasiia Sadybekov, Chen Tian, Cosimo Arnesano, Vsevolod Katritch, Bruce E Herring
The Rho guanine nucleotide exchange factor (RhoGEF) Trio promotes actin polymerization by directly activating the small GTPase Rac1. Recent studies suggest that autism spectrum disorder (ASD)-related behavioral phenotypes in animal models of ASD can be produced by dysregulation of Rac1's control of actin polymerization at glutamatergic synapses. Here, in humans, we discover a large cluster of ASD-related de novo mutations in Trio's Rac1 activating domain, GEF1. Our study reveals that these mutations produce either hypofunctional or hyperfunctional forms of Trio in rodent neurons in vitro...
September 19, 2017: Nature Communications
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