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https://www.readbyqxmd.com/read/29454667/pten-expression-in-astrocytic-processes-after-spinal-cord-injury
#1
T V Povysheva, Y O Mukhamedshina, A A Rizvanov, Y A Chelyshev
The role of the Rho/ROCK/PTEN signaling pathway in the regulation of astrocyte function for consolidation/stabilization of the synapse has not been thoroughly studied. In this study, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in GFAP-positive astrocytic processes in the ventral horns (VH) of the rat spinal cord has been evaluated in the normal condition and in a delayed period (30 days) after dosed contusion spinal cord injury (SCI) in caudal thoracic segments. In intact rats and at 30 days post-injury (dpi), semi-quantitative immunohistochemical analysis showed that there is approximately 2 folds less synaptophysin reactivity in the motoneuron perikarya than outside the perikarya, i...
February 15, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29444449/dendritic-spine-density-and-ephrinb2-levels-of-hippocampal-and-anterior-cingulate-cortex-neurons-increase-sequentially-during-formation-of-recent-and-remote-fear-memory-in-the-mouse
#2
Georgia Abate, Sandra Colazingari, Alessandra Accoto, David Conversi, Arturo Bevilacqua
Memory consolidation is a dynamic process that involves a sequential remodeling of hippocampal-cortical circuits. Although synaptic events underlying memory consolidation are well assessed, fine molecular events controlling this process deserve further characterization. To this aim, we challenged male C57BL/6N mice in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7 days or 36 days later. Mice displayed a strong fear response at all time points with an increase in dendritic spine density and protein levels of the cell adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post conditioning (p...
February 11, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29432803/learning-and-memory-is-modulated-by-cannabidiol-when-administered-during-trace-fear-conditioning
#3
A L Uhernik, Z T Montoya, C D Balkissoon, J P Smith
Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD). Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD...
February 9, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29411265/rare-risk-variants-identification-by-identity-by-descent-mapping-and-whole-exome-sequencing-implicates-neuronal-development-pathways-in-schizophrenia-and-bipolar-disorder
#4
C Salvoro, S Bortoluzzi, A Coppe, G Valle, E Feltrin, M L Mostacciuolo, G Vazza
Schizophrenia (SCZ) and bipolar disorder (BPD) are highly heritable disorders with an estimated co-heritability of 68%. Hundreds of common alleles have been implicated, but recently a role for rare, high-penetrant variants has been also suggested in both disorders. This study investigated a familial cohort of SCZ and BPD patients from a closed population sample, where the high recurrence of the disorders and the homogenous genetic background indicate a possible enrichment in rare risk alleles. A total of 230 subjects (161 cases, 22 unaffected relatives, and 47 controls) were genetically investigated through an innovative strategy that integrates identity-by-descent (IBD) mapping and whole-exome sequencing (WES)...
February 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29396406/dlgap1-knockout-mice-exhibit-alterations-of-the-postsynaptic-density-and-selective-reductions-in-sociability
#5
M P Coba, M J Ramaker, E V Ho, S L Thompson, N H Komiyama, S G N Grant, J A Knowles, S C Dulawa
The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29385102/preventive-effects-of-resveratrol-on-endocannabinoid-system-and-synaptic-protein-modifications-in-rat-cerebral-cortex-challenged-by-bilateral-common-carotid-artery-occlusion-and-reperfusion
#6
Gianfranca Carta, Laura Poddighe, Maria Pina Serra, Marianna Boi, Tiziana Melis, Sara Lisai, Elisabetta Murru, Laura Muredda, Maria Collu, Sebastiano Banni, Marina Quartu
This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT) in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R) and to investigate RVT's ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle), while the second half received the vehicle alone...
January 31, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29384407/effect-of-aucubin-on-neural-precursor-cell-survival-during-neuronal-differentiation
#7
Miyeoun Song, Maeum Han, Yunhee Kim Kwon
Aucubin (ACB) is an iridoid glycoside with various biological activities. Previously it is reported that ACB reduces cell survival and proliferation in many human tumors, whereas it facilitates cell survival and neuroprotection in damaged neuronal cells and disease models. However, its effects on cell survival in the non-proliferating or differentiated neurons are not known. We examined whether ACB facilitated cell survival in differentiating neural precursor cells, HiB5, compared with the proliferating HiB5 cells at various concentrations...
January 31, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29353084/creating-diverse-synapses-from-the-same-molecules
#8
REVIEW
Zoltan Nusser
Research over the past half a century has revealed remarkable diversity among chemical synapses of the CNS. The structural, functional and molecular diversity of synapses was mainly concluded from studying different synapses in distinct brain regions and preparations. It is not surprising that synapses made by molecularly distinct pre-synaptic and post-synaptic cells display different morphological and functional properties with distinct underlying molecular mechanisms. However, synapses made by a single presynaptic cell onto distinct types of postsynaptic cells, or distinct presynaptic inputs onto a single postsynaptic cell, also show remarkable heterogeneity...
January 17, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29343737/moderate-decline-in-select-synaptic-markers-in-the-prefrontal-cortex-ba9-of-patients-with-alzheimer-s-disease-at-various-cognitive-stages
#9
Odile Poirel, Sébastien Mella, Catherine Videau, Lauriane Ramet, Maria Antonietta Davoli, Etienne Herzog, Pavel Katsel, Naguib Mechawar, Vahram Haroutunian, Jacques Epelbaum, Stéphanie Daumas, Salah El Mestikawy
Synaptic loss, plaques and neurofibrillary tangles are viewed as hallmarks of Alzheimer's disease (AD). This study investigated synaptic markers in neocortical Brodmann area 9 (BA9) samples from 171 subjects with and without AD at different levels of cognitive impairment. The expression levels of vesicular glutamate transporters (VGLUT1&2), glutamate uptake site (EAAT2), post-synaptic density protein of 95 kD (PSD95), vesicular GABA/glycine transporter (VIAAT), somatostatin (som), synaptophysin and choline acetyl transferase (ChAT) were evaluated...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335778/hippocampal-area-ca2-properties-and-contribution-to-hippocampal-function
#10
REVIEW
Vincent Robert, Sadiyah Cassim, Vivien Chevaleyre, Rebecca A Piskorowski
This review focuses on area CA2 of the hippocampus, as recent results have revealed the unique properties and surprising role of this region in encoding social, temporal and contextual aspects of memory. Originally identified and described by Lorente de No, in 1934, this region of the hippocampus has unique intra-and extra-hippocampal connectivity, sending and receiving input to septal and hypothalamic regions. Recent in vivo studies have indicated that CA2 pyramidal neurons encode spatial information during immobility and play an important role in the generation of sharp-wave ripples...
January 15, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29321508/thrombospondin-1-secreted-by-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-rescues-neurons-from-synaptic-dysfunction-in-alzheimer-s-disease-model
#11
Dong Hyun Kim, Hoon Lim, Dahm Lee, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Jeong Su Oh, Hyun Ho Hwang, Hong Bae Jeon
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Aβ42-treated mouse hippocampal neurons...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317733/in-vivo-sted-microscopy-visualizes-psd95-sub-structures-and-morphological-changes-over-several-hours-in-the-mouse-visual-cortex
#12
Waja Wegner, Alexander C Mott, Seth G N Grant, Heinz Steffens, Katrin I Willig
The post-synaptic density (PSD) is an electron dense region consisting of ~1000 proteins, found at the postsynaptic membrane of excitatory synapses, which varies in size depending upon synaptic strength. PSD95 is an abundant scaffolding protein in the PSD and assembles a family of supercomplexes comprised of neurotransmitter receptors, ion channels, as well as signalling and structural proteins. We use superresolution STED (STimulated Emission Depletion) nanoscopy to determine the size and shape of PSD95 in the anaesthetised mouse visual cortex...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315422/dietary-therapy-restores-glutamatergic-input-to-orexin-hypocretin-neurons-after-traumatic-brain-injury-in-mice
#13
Jonathan E Elliott, Samuel E De Luche, Madeline J Churchill, Cindy Moore, Akiva S Cohen, Charles K Meshul, Miranda M Lim
Study Objectives: In previous work, dietary branched chain amino acid (BCAA) supplementation, precursors to de novo glutamate and gamma-aminobutyric acid (GABA) synthesis, restored impaired sleep-wake regulation and orexin neuronal activity post-traumatic brain injury (TBI) in mice. TBI was speculated to reduce orexin neuronal activity through decreased regional excitatory (glutamate) and/or increased inhibitory (GABA) input. Therefore, we hypothesized TBI would decrease synaptic glutamate and/or increase synaptic GABA in nerve terminals contacting orexin neurons, and BCAA supplementation would restore TBI-induced changes in synaptic glutamate and/or GABA...
January 5, 2018: Sleep
https://www.readbyqxmd.com/read/29297151/liver-x-receptor-agonist-gw3965-regulates-synaptic-function-upon-amyloid-beta-exposure-in-hippocampal-neurons
#14
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29281827/synaptic-targeting-and-function-of-sapaps-mediated-by-phosphorylation-dependent-binding-to-psd-95-maguks
#15
Jinwei Zhu, Qingqing Zhou, Yuan Shang, Hao Li, Mengjuan Peng, Xiao Ke, Zhuangfeng Weng, Rongguang Zhang, Xuhui Huang, Shawn S C Li, Guoping Feng, Youming Lu, Mingjie Zhang
The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29274095/alterations-in-ca1-hippocampal-synapses-in-a-mouse-model-of-fragile-x-syndrome
#16
Safdar Jawaid, Grahame J Kidd, Jing Wang, Carrie Swetlik, Ranjan Dutta, Bruce D Trapp
Fragile X Syndrome (FXS) is the major cause of inherited mental retardation and the leading genetic cause of Autism spectrum disorders. FXS is caused by mutations in the Fragile X Mental Retardation 1 (Fmr1) gene, which results in transcriptional silencing of Fragile X Mental Retardation Protein (FMRP). To elucidate cellular mechanisms involved in the pathogenesis of FXS, we compared dendritic spines in the hippocampal CA1 region of adult wild-type (WT) and Fmr1 knockout (Fmr1-KO) mice. Using diolistic labeling, confocal microscopy, and three-dimensional electron microscopy, we show a significant increase in the diameter of secondary dendrites, an increase in dendritic spine density, and a decrease in mature dendritic spines in adult Fmr1-KO mice...
December 23, 2017: Glia
https://www.readbyqxmd.com/read/29234273/indirubin-derivative-7-bromoindirubin-3-oxime-7bio-attenuates-a%C3%AE-oligomer-induced-cognitive-impairments-in-mice
#17
Liping Chen, Chunhui Huang, Jieyi Shentu, Minjun Wang, Sicheng Yan, Fei Zhou, Zaijun Zhang, Chuang Wang, Yifan Han, Qinwen Wang, Wei Cui
Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29215028/effect-of-canola-oil-consumption-on-memory-synapse-and-neuropathology-in-the-triple-transgenic%C3%A2-mouse-model-of-alzheimer-s-disease
#18
Elisabetta Lauretti, Domenico Praticò
In recent years consumption of canola oil has increased due to lower cost compared with olive oil and the perception that it shares its health benefits. However, no data are available on the effect of canola oil intake on Alzheimer's disease (AD) pathogenesis. Herein, we investigated the effect of chronic daily consumption of canola oil on the phenotype of a mouse model of AD that develops both plaques and tangles (3xTg). To this end mice received either regular chow or a chow diet supplemented with canola oil for 6 months...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29163080/behavioral-and-neurochemical-phenotyping-of-mice-incapable-of-homer1a-induction
#19
Michael C Datko, Jia-Hua Hu, Melanie Williams, Cindy M Reyes, Kevin D Lominac, Georg von Jonquieres, Matthias Klugmann, Paul F Worley, Karen K Szumlinski
Immediate early and constitutively expressed products of the Homer1 gene regulate the functional assembly of post-synaptic density proteins at glutamatergic synapses to influence excitatory neurotransmission and synaptic plasticity. Earlier studies of Homer1 gene knock-out (KO) mice indicated active, but distinct, roles for IEG and constitutively expressed Homer1 gene products in regulating cognitive, emotional, motivational and sensorimotor processing, as well as behavioral and neurochemical sensitivity to cocaine...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#20
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
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