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https://www.readbyqxmd.com/read/28730825/the-implication-of-ampa-receptor-in-synaptic-plasticity-impairment-and-intellectual-disability-in-fragile-x-syndrome
#1
G-R Cheng, X-Y Li, Y-D Xiang, D Liu, S M McClintock, Y Zeng
Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28729535/pld1-promotes-dendritic-spine-development-by-inhibiting-adam10-mediated-n-cadherin-cleavage
#2
Li-Da Luo, Gang Li, Yun Wang
Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer's disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729445/preferential-disruption-of-prefrontal-gabaergic-function-by-nanomolar-concentrations-of-the-%C3%AE-7nach-negative-modulator-kynurenic-acid
#3
Eden Flores-Barrera, Daniel R Thomases, Daryn K Cass, Ajay Bhandari, Robert Schwarcz, John P Bruno, Kuei Y Tseng
Increased concentrations of kynurenic acid (KYNA) in the prefrontal cortex (PFC) are thought to contribute to the development of cognitive deficits observed in schizophrenia. Although this view is consistent with pre-clinical studies showing a negative impact of prefrontal KYNA elevation on executive function, the mechanism underlying such a disruption remains unclear. Here we measured changes in local field potential responses to ventral hippocampal stimulation in vivo, and conducted whole-cell patch-clamp recordings in brain slices to reveal how nanomolar concentrations of KYNA alter synaptic transmission in the PFC of male adult rats...
July 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28724954/loss-of-x-linked-protocadherin-19-differentially-affects-the-behavior-of-heterozygous-female-and-hemizygous-male-mice
#4
Shuichi Hayashi, Yoko Inoue, Satoko Hattori, Mari Kaneko, Go Shioi, Tsuyoshi Miyakawa, Masatoshi Takeichi
Mutations in the X-linked gene Protocadherin-19 (Pcdh19) cause female-limited epilepsy and mental retardation in humans. Although Pcdh19 is known to be a homophilic cell-cell adhesion molecule, how its mutations bring about female-specific disorders remains elusive. Here, we report the effects of Pcdh19 knockout in mice on their development and behavior. Pcdh19 was expressed in various brain regions including the cerebral cortex and hippocampus. Although Pcdh19-positive cells were evenly distributed in layer V of wild-type cortices, their distribution became a mosaic in Pcdh19 heterozygous female cortices...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#5
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28720382/activated-leukocyte-cell-adhesion-molecule-is-involved-in-excitatory-synaptic-transmission-and-plasticity-in-the-rat-spinal-dorsal-horn
#6
Eun-Sung Park, Sang-Min Jeon, Haein Weon, Hee-Jung Cho, Dong-Ho Youn
Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH...
July 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28720317/dcc-receptors-drive-prefrontal-cortex-maturation-by-determining-dopamine-axon%C3%A2-targeting-in-adolescence
#7
Lauren M Reynolds, Matthew Pokinko, Angélica Torres-Berrío, Santiago Cuesta, Laura C Lambert, Esther Del Cid Pellitero, Michael Wodzinski, Colleen Manitt, Paul Krimpenfort, Bryan Kolb, Cecilia Flores
BACKGROUND: Dopaminergic input to the prefrontal cortex (PFC) increases throughout adolescence and, by establishing precisely localized synapses, calibrates cognitive function. However, why and how mesocortical dopamine axon density increases across adolescence remains unknown. METHODS: We used a developmental application of axon-initiated recombination to label and track the growth of dopamine axons across adolescence in mice. We then paired this recombination with cell-specific knockdown of the netrin-1 receptor DCC to determine its role in adolescent dopamine axon growth...
June 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28716964/a-glun2b-selective-nmdar-antagonist-reverses-synapse-loss-and-cognitive-impairment-produced-by-the-hiv-1-protein-tat
#8
Jonathan D Raybuck, Nicholas J Hargus, Stanley A Thayer
HIV-associated neurocognitive disorder (HAND) affects approximately half of HIV-infected patients. Loss of synaptic connections is a hallmark of many neurocognitive disorders, including HAND. The HIV-1 protein transactivator of transcription (Tat) disrupts synaptic connections both in vitro and in vivo and has been linked to impaired neurocognitive function in humans. In vitro studies have shown that ifenprodil, an antagonist selective for GluN2B-containing NMDARs, reverses synapse loss when applied after Tat...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28712672/noise-induced-cochlear-synaptopathy-in-rhesus-monkeys-macaca-mulatta
#9
M D Valero, J A Burton, S N Hauser, T A Hackett, R Ramachandran, M C Liberman
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss...
July 8, 2017: Hearing Research
https://www.readbyqxmd.com/read/28711710/comparison-of-the-role-of-metabotropic-glutamate-receptor-subtype-1-in-developmental-refinement-of-neuronal-connectivity-between-the-cerebellum-and-the-sensory-thalamus
#10
REVIEW
Madoka Narushima
Developmental refinement of neuronal connectivity is crucial for proper brain function. In the early phase of development, input fibers arrive at their target areas guided by specific molecular cues and form abundant immature synapses. Then, functionally important synapses are preserved and strengthened by neural activity while unnecessary synapses are eliminated. Afferent synapses in the sensory thalamus, such as from retina to lateral geniculate nucleus, and climbing fiber (CF)-Purkinje cell (PC) synapses in the cerebellum are valuable models for studying this developmental refinement of synaptic connectivity because only a limited number of input fibers innervate a given postsynaptic thalamocortical (TC) neuron or PC...
July 12, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28711300/raft-dependent-endocytic-movement-and-intracellular-cluster-formation-during-t%C3%A2-cell-activation-triggered-by-concanavalin-a
#11
Satomi Yabuuchi, Satoshi Endo, KeangOk Baek, Kunihide Hoshino, Yoshio Tsujino, Mun'delanji C Vestergaard, Masahiro Takagi
Certain food ingredients can stimulate the human immune system. A lectin, concanavalin A (ConA), from Canavalia ensiformis (jack bean) is one of the most well-known food-derived immunostimulants and mediates activation of cell-mediated immunity through T cell proliferation. Generally, T cell activation is known to be triggered by the interaction between T cells and antigen-presenting cells (APCs) via a juxtacrine (contact-dependent) signaling pathway. The mechanism has been well characterized and is referred to as formation of the immunological synapse (IS)...
July 12, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28706739/emulation-with-organic-memristive-devices-of-impairment-of-ltp-mechanism-in-neurodegenerative-disease-pathology
#12
Silvia Battistoni, Victor Erokhin, Salvatore Iannotta
We explore and demonstrate the extension of the synapse-mimicking properties of memristive devices to a dysfunctional synapse as it occurs in the Alzheimer's disease (AD) pathology. The ability of memristive devices to reproduce synapse properties such as LTP, LTD, and STDP has been already widely demonstrated, and moreover, they were used for developing artificial neuron networks (perceptrons) able to simulate the information transmission in a cell network. However, a major progress would be to extend the common sense of neuromorphic device even to the case of dysfunction of natural synapses...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28703129/precise-inhibitory-microcircuit-assembly-of-developmentally-related-neocortical-interneurons-in-clusters
#13
Xin-Jun Zhang, Zhizhong Li, Zhi Han, Khadeejah T Sultan, Kun Huang, Song-Hai Shi
GABA-ergic interneurons provide diverse inhibitions that are essential for the operation of neuronal circuits in the neocortex. However, the mechanisms that control the functional organization of neocortical interneurons remain largely unknown. Here we show that developmental origins influence fine-scale synapse formation and microcircuit assembly of neocortical interneurons. Spatially clustered neocortical interneurons originating from low-titre retrovirus-infected radial glial progenitors in the embryonic medial ganglionic eminence and preoptic area preferentially develop electrical, but not chemical, synapses with each other...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28702161/bio-collections-in-autism-research
#14
REVIEW
Jamie Reilly, Louise Gallagher, June L Chen, Geraldine Leader, Sanbing Shen
Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with diverse clinical manifestations and symptoms. In the last 10 years, there have been significant advances in understanding the genetic basis for ASD, critically supported through the establishment of ASD bio-collections and application in research. Here, we summarise a selection of major ASD bio-collections and their associated findings. Collectively, these include mapping ASD candidate genes, assessing the nature and frequency of gene mutations and their association with ASD clinical subgroups, insights into related molecular pathways such as the synapses, chromatin remodelling, transcription and ASD-related brain regions...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28696431/synaptic-activity-protects-against-ad-and-ftd-like-pathology-via-autophagic-lysosomal-degradation
#15
Y Akwa, E Gondard, A Mann, E Capetillo-Zarate, E Alberdi, C Matute, S Marty, T Vaccari, A M Lozano, E E Baulieu, D Tampellini
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28695547/human-immunodeficiency-virus-promotes-mitochondrial-toxicity
#16
REVIEW
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Margarita Trejo, Hoai T Ton, Gerard P Ahern, Italo Mocchetti
Combined antiretroviral therapies (cART) have had remarkable success in reducing morbidity and mortality among patients infected with human immunodeficiency virus (HIV). However, mild forms of HIV-associated neurocognitive disorders (HAND), characterized by loss of synapses, remain. cART may maintain an undetectable HIV RNA load but does not eliminate the expression of viral proteins such as trans-activator of transcription (Tat) and the envelope glycoprotein gp120 in the brain. These two viral proteins are known to promote synaptic simplifications by several mechanisms, including alteration of mitochondrial function and dynamics...
July 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28695538/fgf9-y162c-mutation-alters-information-processing-and-social-memory-in-mice
#17
Lillian Garrett, Lore Becker, Jan Rozman, Oliver Puk, Tobias Stoeger, Ali Önder Yildirim, Alexander Bohla, Oliver Eickelberg, Wolfgang Hans, Cornelia Prehn, Jerzy Adamski, Thomas Klopstock, Ildikó Rácz, Andreas Zimmer, Martin Klingenspor, Helmut Fuchs, Valerie Gailus-Durner, Wolfgang Wurst, Martin Hrabě de Angelis, Jochen Graw, Sabine M Hölter
In neuropsychiatric diseases, such as major depression and anxiety, pathogenic vulnerability is partially dictated by a genetic predisposition. The search continues to define this genetic susceptibility and establish new genetic elements as potential therapeutic targets. The fibroblast growth factors (FGFs) could be interesting in this regard. This family of signaling molecules plays important roles in development while also functioning within the adult. This includes effects on aspects of brain function such as neurogenesis and synapse formation...
July 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28694772/connexin-dependent-neuroglial-networking-as-a-new-therapeutic-target
#18
REVIEW
Mathieu Charvériat, Christian C Naus, Luc Leybaert, Juan C Sáez, Christian Giaume
Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28694464/monocular-deprivation-induces-dendritic-spine-elimination-in-the-developing-mouse-visual-cortex
#19
Yanmei Zhou, Baoling Lai, Wen-Biao Gan
It is well established that visual deprivation has a profound impact on the responsiveness of neurons in the developing visual cortex. The effect of visual deprivation on synaptic connectivity remains unclear. Using transcranial two-photon microscopy, we examined the effect of visual deprivation and subsequent recovery on dendritic spine remodeling of layer 5 pyramidal neurons in the mouse primary visual cortex. We found that monocular deprivation (MD), but not binocular deprivation (BD), increased dendritic spine elimination over 3 days in the binocular region of 4-week-old adolescent mice...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693467/predicting-rna-hyper-editing-with-a-novel-tool-when-unambiguous-alignment-is-impossible
#20
Wilson H McKerrow, Yiannis A Savva, Ali Rezaei, Robert A Reenan, Charles E Lawrence
BACKGROUND: Repetitive elements are now known to have relevant cellular functions, including self-complementary sequences that form double stranded (ds) RNA. There are numerous pathways that determine the fate of endogenous dsRNA, and misregulation of endogenous dsRNA is a driver of autoimmune disease, particularly in the brain. Unfortunately, the alignment of high-throughput, short-read sequences to repeat elements poses a dilemma: Such sequences may align equally well to multiple genomic locations...
July 10, 2017: BMC Genomics
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