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https://www.readbyqxmd.com/read/28088287/insulin-like-growth-factor-binding-protein-3-deficiency-leads-to-behavior-impairment-with-monoaminergic-and-synaptic-dysfunction
#1
Hongmei Dai, Yu-Ichi Goto, Masayuki Itoh
Insulin-like growth factor binding protein (IGFBP)-3 regulates IGF bioactivity, induces apoptosis, and inhibits cell growth independent of IGFs, but the functional role of IGFBP3 in the brain is not clear. In the present study, we revealed the effect of IGFBP3 on the brain by characterizing the phenotype of Igfbp3-null mice. Compared with wild-type mice, Igfbp3-null mice had significantly decreased IGF-1 content in the brain but no change in weights of brain and body. In Igfbp3-null mice, the number of dendritic spines was significantly reduced, and the dendritic diameter was thickening...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#2
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#3
Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista, Flávia Carvalho Alcantara Gomes
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28036092/human-rho-guanine-nucleotide-exchange-factor-11-arhgef11-regulates-dendritic-morphogenesis
#4
Yutaka Mizuki, Manabu Takaki, Shinji Sakamoto, Sojiro Okamoto, Makiko Kishimoto, Yuko Okahisa, Masahiko Itoh, Norihito Yamada
Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance. ARHGEF11 variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035673/somatic-and-neuritic-spines-on-tyrosine-hydroxylase-immunopositive-cells-of-rat-retina
#5
Anna Fasoli, James Dang, Aaron H Gouw, Jeffrey S Johnson, Alex Fogli Iseppe, Andrew T Ishida
Dopamine- and tyrosine hydroxylase-immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata which release dopamine when exposed to glutamate receptor agonists...
December 30, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28025327/fmrp-dependent-mdm2-dephosphorylation-is-required-for-mef2-induced-synapse-elimination
#6
Nien-Pei Tsai, Julia R Wilkerson, Weirui Guo, Kimberly M Huber
The Myocyte Enhancer Factor 2 (MEF2) transcription factors suppress an excitatory synapse number by promoting degradation of the synaptic scaffold protein, postsynaptic density protein 95 (PSD-95), a process that is deficient in the mouse model of Fragile X Syndrome, Fmr1 KO. How MEF2 activation results in PSD-95 degradation and why this is defective in Fmr1 KO neurons is unknown. Here we report that MEF2 induces a Protein phosphatase 2A (PP2A)-mediated dephosphorylation of murine double minute-2 (Mdm2), the ubiquitin E3 ligase for PSD-95, which results in nuclear export and synaptic accumulation of Mdm2 as well as PSD-95 degradation and synapse elimination...
December 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28012021/lentiviral-modulation-of-wnt-%C3%AE-catenin-signaling-affects-in-vivo-ltp
#7
Olga Ya Ivanova, Yulia V Dobryakova, Sergey V Salozhin, Viktor A Aniol, Mikhail V Onufriev, Natalia V Gulyaeva, Vladimir A Markevich
Wnt signaling is involved in hippocampal development and synaptogenesis. Numerous recent studies have been focused on the role of Wnt ligands in the regulation of synaptic plasticity. Inhibitors and activators of canonical Wnt signaling were demonstrated to decrease or increase, respectively, in vitro long-term potentiation (LTP) maintenance in hippocampal slices (Chen et al. in J Biol Chem 281:11910-11916, 2006; Vargas et al. in J Neurosci 34:2191-2202, 2014, Vargas et al. in Exp Neurol 264:14-25, 2015). Using lentiviral approach to down- and up-regulate the canonical Wnt signaling, we explored whether Wnt/β-catenin signaling is critical for the in vivo LTP...
December 23, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28002633/vta-da-neuron-excitatory-synapses-in-shank3-%C3%AE-ex-4-9-mouse-line
#8
Bariselli Sebastiano, Bellone Camilla
SHANK3 proteins belong to the Shank/ProSAP family, which contain five-conserved domains - the ankyrin (ANK) repeated, the Src homology 3 (SH3), the PSD-95/Discs large/ZO-1 (PDZ), the proline-rich and the sterile alpha motif (SAM; Sheng and Kim, 2000). SHANK proteins are located at the postsynaptic density of excitatory synapses and indirectly link the metabotropic (mGluRs) and the ionotropic glutamate receptor (iGluRs: AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and NMDARs, N-methyl-D-aspartate receptors) via different domains (Naisbitt et al...
December 21, 2016: Synapse
https://www.readbyqxmd.com/read/27997694/spatial-patterning-of-excitatory-and-inhibitory-neuropil-territories-during-spinal-circuit-development
#9
Qing Yan, Lu Zhai, Bo Zhang, Julia E Dallman
To generate rhythmic motor behaviors, both single neurons and neural circuits require a balance between excitatory inputs that trigger action potentials and inhibitory inputs that promote a stable resting potential (E/I balance). Previous studies have focused on individual neurons and have shown that, over a short spatial scale, excitatory and inhibitory (E/I) synapses tend to form structured territories with inhibitory inputs enriched on cell bodies and proximal dendrites and excitatory inputs on distal dendrites...
December 20, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27993509/reggie-1-and-reggie-2-flotillins-participate-in-rab11a-dependent-cargo-trafficking-spine-synapse-formation-and-ltp-related-ampa-receptor-glua1-surface-exposure-in-mouse-hippocampal-neurons
#10
Vsevolod Bodrikov, Aline Pauschert, Gaga Kochlamazashvili, Claudia A O Stuermer
Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rab11a the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rab11a may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k...
December 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27984133/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#11
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
October 29, 2016: Toxicology
https://www.readbyqxmd.com/read/27974193/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#12
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27966487/expressions-of-visual-pigments-and-synaptic-proteins-in-neonatal-chick-retina-exposed-to-light-of-variable-photoperiods
#13
Kumar Abhiram Jha, Tapas C Nag, Shashi Wadhwa, Tara Sankar Roy
Light causes damage to the retina, which is one of the supposed factors for age-related macular degeneration in human. Some animal species show drastic retinal changes when exposed to intense light (e.g. albino rats). Although birds have a pigmented retina, few reports indicated its susceptibility to light damage. To know how light influences a cone-dominated retina (as is the case with human), we examined the effects of moderate light intensity on the retina of white Leghorn chicks (Gallus g. domesticus). The newly hatched chicks were initially acclimatized at 500 lux for 7 days in 12 h light: 12 h dark cycles (12L:12D)...
December 2016: Journal of Biosciences
https://www.readbyqxmd.com/read/27965538/lack-of-cdkl5-disrupts-the-organization-of-excitatory-and-inhibitory-synapses-and-parvalbumin-interneurons-in-the-primary-visual-cortex
#14
Riccardo Pizzo, Antonia Gurgone, Enrico Castroflorio, Elena Amendola, Cornelius Gross, Marco Sassoè-Pognetto, Maurizio Giustetto
Cyclin-dependent kinase-like 5 (CDKL5) mutations are found in severe neurodevelopmental disorders, including the Hanefeld variant of Rett syndrome (RTT; CDKL5 disorder). CDKL5 loss-of-function murine models recapitulate pathological signs of the human disease, such as visual attention deficits and reduced visual acuity. Here we investigated the cellular and synaptic substrates of visual defects by studying the organization of the primary visual cortex (V1) of Cdkl5(-/y) mice. We found a severe reduction of c-Fos expression in V1 of Cdkl5(-/y) mutants, suggesting circuit hypoactivity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27935149/the-sorting-receptor-sorcs3-is-a-stronger-regulator-of-glutamate-receptor-functions-compared-to-gabaergic-mechanisms-in-the-hippocampus
#15
Gitte B Christiansen, Katrine Andersen, Sarah Riis, Anders Nykjaer, Ulrik Bølcho, Morten Skovgaard Jensen, Mai Marie Holm
Correct function of glutamate receptors in the postsynaptic density is crucial to synaptic function and plasticity. SorCS3 (sortilin-related receptor CNS expressed 3) is a sorting receptor which previously has been shown to interact with the key postsynaptic proteins; PSD-95 and PICK1. In this study, we employed electrophysiological analyses of acute brain slices combined with immunohistochemistry to define the role of SorCS3 in hippocampal synapses in CA1 and the dentate gyrus. We analyzed a juvenile (P17-21) and a young adult (P55-65) group of animals from a Sorcs3 knockout mouse model...
December 9, 2016: Hippocampus
https://www.readbyqxmd.com/read/27900211/in-vivo-expression-of-reprogramming-factors-increases-hippocampal-neurogenesis-and-synaptic-plasticity-in-chronic-hypoxic-ischemic-brain-injury
#16
Soohyun Wi, Ji Hea Yu, MinGi Kim, Sung-Rae Cho
Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27894930/sex-dependent-influence-of-chronic-mild-stress-cms-on-voluntary-alcohol-consumption-study-of-neurobiological-consequences
#17
Eva M Marco, Javier Antonio Ballesta, Carlos Irala, María-Donina Hernández, María Elisa Serrano, Virginia Mela, Meritxell López-Gallardo, María-Paz Viveros
Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males...
January 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27878552/strength-and-aerobic-exercises-improve-spatial-memory-in-aging-rats-through-stimulating-distinct-neuroplasticity-mechanisms
#18
Thais Ceresér Vilela, Alexandre Pastoris Muller, Adriani Paganini Damiani, Tamires Pavei Macan, Sabrina da Silva, Paula Bortoluzzi Canteiro, Alisson de Sena Casagrande, Giulia Dos Santos Pedroso, Renata Tiscoski Nesi, Vanessa Moraes de Andrade, Ricardo Aurino de Pinho
Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27867342/the-family-of-crumbs-genes-and-human-disease
#19
REVIEW
Anne M Slavotinek
The family of vertebrate Crumbs proteins, homologous to Drosophila Crumbs (Crb), share large extracellular domains with epidermal growth factor-like repeats and laminin-globular domains, a single transmembrane domain, and a short intracellular C-terminus containing a single membrane proximal 4.1/ezrin/radixin/moesin-binding domain and PSD-95/Discs large/ZO-1-binding motifs. There are 3 Crb genes in humans - Crumbs homolog-1 (CRB1), Crumbs homolog-2 (CRB2), and Crumbs homolog-3 (CRB3). Bilallelic loss-of-function mutations in CRB1 cause visual impairment, with Leber's congenital amaurosis and retinitis pigmentosa, whereas CRB2 mutations are associated with raised maternal serum and amniotic fluid alpha feto-protein levels, ventriculomegaly/hydrocephalus, and renal disease, ranging from focal segmental glomerulosclerosis to congenital Finnish nephrosis...
October 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27861918/maguk-dynamics-reveal-regional-and-developmental-specificity-of-synapse-stability
#20
Jonathan M Levy, Roger A Nicoll
Fast excitatory transmission in the brain requires localization of glutamate receptors to synapses. The MAGUK family of synaptic scaffolding proteins is critical for localization of glutamate receptors to synapses. Although the MAGUKs are well-studied in reduced preparations and young animals, little data exists on their role in adult animals. Here, we present a detailed developmental study of the role of the MAGUKs during rat development. We first confirm by knockdown experiments that MAGUKs are essential for glutamatergic transmission in young animals and cultured slices, and increases in PSD-95 by overexpression causes correlated increases in glutamatergic transmission...
November 8, 2016: Journal of Physiology
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