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https://www.readbyqxmd.com/read/28934273/novel-derivative-of-paeonol-paeononlsilatie-sodium-alleviates-behavioral-damage-and-hippocampal-dendritic-injury-in-alzheimer-s-disease-concurrent-with-cofilin1-phosphorylated-cofilin1-and-rac1-cdc42-alterations-in-rats
#1
Fei Han, Ting-Ting Zhuang, Jing-Jing Chen, Xiu-Ling Zhu, Ya-Fei Cai, Ya-Ping Lu
Alzheimer's disease (AD) is a typical hippocampal amnesia and the most common senile dementia. Many studies suggest that cognitive impairments are more closely correlated with synaptic loss than the burden of amyloid deposits in AD progression. To date, there is no effective treatment for this disease. Paeonol has been widely employed in traditional Chinese medicine. This compound improves learning behavior in an animal model; however, the mechanism remains unclear. In this study, Paeononlsilatie sodium (Pa), a derivative of Paeonol, attenuated D-galactose (D-gal) and AlCl3-induced behavioral damages in rats based on evaluations of the open field test (OFT), elevated plus maze test (EPMT), and Morris water maze test (MWMT)...
2017: PloS One
https://www.readbyqxmd.com/read/28931811/distal-axotomy-enhances-retrograde-presynaptic-excitability-onto-injured-pyramidal-neurons-via-trans-synaptic-signaling
#2
Tharkika Nagendran, Rylan S Larsen, Rebecca L Bigler, Shawn B Frost, Benjamin D Philpot, Randolph J Nudo, Anne Marion Taylor
Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28929566/protracted-dendritic-growth-in-the-typically-developing-human-amygdala-and-increased-spine-density-in-young-asd-brains
#3
R K Weir, M D Bauman, B Jacobs, C M Schumann
The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: 1) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and 2), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood...
September 20, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28928633/glutaminase-and-mmp-9-downregulation-in-cortex-and-hippocampus-of-lpa1-receptor-null-mice-correlate-with-altered-dendritic-spine-plasticity
#4
Ana Peñalver, José A Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, Mercedes Martín-Rufián, Guillermo Estivill-Torrús, Raquel Sánchez-Varo, Francisco J Alonso, Mercedes Pérez-Hernández, María I Colado, Antonia Gutiérrez, Fernando Rodríguez de Fonseca, Javier Márquez
Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28928015/dendritic-homeostasis-disruption-in-a-novel-frontotemporal-dementia-mouse-model-expressing-cytoplasmic-fused-in-sarcoma
#5
Gen Shiihashi, Daisuke Ito, Itaru Arai, Yuki Kobayashi, Kanehiro Hayashi, Shintaro Otsuka, Kazunori Nakajima, Michisuke Yuzaki, Shigeyoshi Itohara, Norihiro Suzuki
Cytoplasmic aggregation of fused in sarcoma (FUS) is detected in brain regions affected by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which compose the disease spectrum, FUS proteinopathy. To understand the pathomechanism of ALS-FTD-associated FUS, we examined the behavior and cellular properties of an ALS mouse model overexpressing FUS with nuclear localization signal deletion. Mutant FUS transgenic mice showed hyperactivity, social interactional deficits, and impaired fear memory retrieval, all of which are compatible with FTD phenotypes...
September 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28926161/neural-basis-of-major-depression-beyond-monoamine-hypothesis
#6
Shuken Boku, Shin Nakagawa, Hiroyuki Toda, Akitoyo Hishimoto
Monoamine hypothesis has been accepted as the most common hypothesis of major depression for a long period because of its simplicity and understandability. Actually, most of currently used antidepressants have been considered to act based on monoamine hypothesis. However, it has been pointed out as an important problem of monoamine hypothesis that it is unable to explain the latency of response to antidepressants. In addition, a large number of patients with major depression has been refractory to currently used antidepressants yet...
September 19, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28924658/two-photon-sted-microscopy-for-nanoscale-imaging-of-neural-morphology-in-vivo
#7
Mirelle J T Ter Veer, Thomas Pfeiffer, U Valentin Nägerl
The advent of super-resolution microscopy offers to bridge the gap between electron and light microscopy. It has opened up the possibility of visualizing cellular structures and dynamic signaling events on the "mesoscale" well below the classic diffraction barrier of light microscopy (10-200 nm), while essentially retaining the advantages of fluorescence microscopy concerning multicolor labeling, detection sensitivity, signal contrast, live-cell imaging, and temporal resolution.From among the new super-resolution techniques, STED microscopy stands out as a laser-scanning imaging modality, which enables nanoscale volume-metric imaging of cellular morphology...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28924236/in-vivo-mouse-and-live-cell-sted-microscopy-of-neuronal-actin-plasticity-using-far-red-emitting-fluorescent-proteins
#8
Waja Wegner, Peter Ilgen, Carola Gregor, Joris van Dort, Alexander C Mott, Heinz Steffens, Katrin I Willig
The study of proteins in dendritic processes within the living brain is mainly hampered by the diffraction limit of light. STED microscopy is so far the only far-field light microscopy technique to overcome the diffraction limit and resolve dendritic spine plasticity at superresolution (nanoscopy) in the living mouse. After having tested several far-red fluorescent proteins in cell culture we report here STED microscopy of the far-red fluorescent protein mNeptune2, which showed best results for our application to superresolve actin filaments at a resolution of ~80 nm, and to observe morphological changes of actin in the cortex of a living mouse...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924188/dopamine-d1-receptor-subtype-mediates-acute-stress-induced-dendritic-growth-in-excitatory-neurons-of-the-medial-prefrontal-cortex-and-contributes-to-suppression-of-stress-susceptibility-in-mice
#9
R Shinohara, M Taniguchi, A T Ehrlich, K Yokogawa, Y Deguchi, Y Cherasse, M Lazarus, Y Urade, A Ogawa, S Kitaoka, A Sawa, S Narumiya, T Furuyashiki
Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28923274/mapping-orbitofrontal-limbic-maturation-in-non-human-primates-a-longitudinal-magnetic-resonance-imaging-study
#10
Akiko Uematsu, Junichi Hata, Yuji Komaki, Fumiko Seki, Chihoko Yamada, Norio Okahara, Yoko Kurotaki, Erika Sasaki, Hideyuki Okano
Brain development involves spatiotemporally complex microstructural changes. A number of neuropsychiatric disorders are linked to the neural processes of development and aging. Thus, it is important to understanding the typical developmental patterns of various brain structures, which will help to define critical periods of vulnerability for neural maturation, as well as anatomical mechanisms of brain structure-related neuropathology. In this study, we used magnetic resonance imaging to assess development of the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus in a non-human primate species, the common marmoset (Callithrix jacchus)...
September 15, 2017: NeuroImage
https://www.readbyqxmd.com/read/28921611/dendritic-spines-provide-cognitive-resilience-against-alzheimer-s-disease
#11
Benjamin D Boros, Kelsey M Greathouse, Erik G Gentry, Kendall A Curtis, Elizabeth L Birchall, Marla Gearing, Jeremy H Herskowitz
OBJECTIVE: Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) initiate years prior to clinical dementia onset. However some 30%-50% of older individuals that harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology structural changes in dendritic spines would distinguish individuals that had or did not have clinical dementia...
September 16, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28912711/increased-hippocampal-probdnf-contributes-to-memory-impairments-in-aged-mice
#12
Mona Buhusi, Chris Etheredge, Ann-Charlotte Granholm, Catalin V Buhusi
Memory decline during aging or accompanying neurodegenerative diseases, represents a major health problem. Neurotrophins have long been considered relevant to the mechanisms of aging-associated cognitive decline and neurodegeneration. Mature Brain-Derived Neurotrophic Factor (BDNF) and its precursor (proBDNF) can both be secreted in response to neuronal activity and exert opposing effects on neuronal physiology and plasticity. In this study, biochemical analyses revealed that increased levels of proBDNF are present in the aged mouse hippocampus relative to young and that the level of hippocampal proBDNF inversely correlates with the ability to perform in a spatial memory task, the water radial arm maze (WRAM)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28911966/fluoxetine-administration-during-adolescence-attenuates-cognitive-and-synaptic-deficits-in-adult-3%C3%A3-tgad-mice
#13
Dong-Sheng Sun, Li-Feng Gao, Li Jin, Hao Wu, Qun Wang, You Zhou, Shuhao Fan, Xia Jiang, Dan Ke, Hao Lei, Jian-Zhi Wang, Gong-Ping Liu
Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; however, the preventive effects of FLX on cognitive impairments in Alzheimer's disease (AD) have not been reported. Here, we studied whether adolescent administration of fluoxetine can prevent memory deficits in AD transgenic mice that harbour PS1m146v, APPswe and TauP301L mutations (3 × TgAD). FLX was applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 consecutive days, and the effects of FLX were observed at 6-month...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28904093/sodium-dynamics-in-pyramidal-neuron-dendritic-spines-synaptically-evoked-entry-predominantly-through-ampa-receptors-and-removal-by-diffusion
#14
Kenichi Miyazaki, William N Ross
Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties with newly developed simultaneous sodium and calcium imaging that had single spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high speed, low noise CCD camera...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28904092/map1b-light-chain-modulates-synaptic-transmission-via-ampa-receptor-intracellular-trapping
#15
Rocío Palenzuela, Yolanda Gutiérrez, Jonathan E Draffin, Argentina Lario, Marion Benoist, José A Esteban
The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein MAP1B, in modulating the access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules that limit vesicular transport...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28900386/altered-developmental-expression-of-the-astrocyte-secreted-factors-hevin-and-sparc-in-the-fragile-x-mouse-model
#16
Jessica Wallingford, Angela L Scott, Kelly Rodrigues, Laurie C Doering
Astrocyte dysfunction has been indicated in many neurodevelopmental disorders, including Fragile X Syndrome (FXS). FXS is caused by a deficiency in fragile X mental retardation protein (FMRP). FMRP regulates the translation of numerous mRNAs and its loss disturbs the composition of proteins important for dendritic spine and synapse development. Here, we investigated whether the astrocyte-derived factors hevin and SPARC, known to regulate excitatory synapse development, have altered expression in FXS. Specifically, we analyzed the expression of these factors in wild-type (WT) mice and in fragile X mental retardation 1 (Fmr1) knock-out (KO) mice that lack FMRP expression...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28900187/electrostatics-of-non-neutral-biological-microdomains
#17
J Cartailler, Z Schuss, D Holcman
Voltage and charge distributions in cellular microdomains regulate communications, excitability, and signal transduction. We report here new electrical laws in a biological cell, which follow from a nonlinear electro-diffusion model. These newly discovered laws derive from the geometrical cell-membrane properties, such as membrane curvature, volume, and surface area. The electro-diffusion laws can now be used to predict and interpret voltage distribution in cellular microdomains such as synapses, dendritic spine, cilia and more...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899992/depletion-of-progranulin-reduces-glun2b-containing-nmda-receptor-density-tau-phosphorylation-and-dendritic-arborization-in-mouse-primary-cortical-neurons
#18
Francesca Longhena, Michela Zaltieri, Jessica Grigoletto, Gaia Faustini, Luca La Via, Roberta Ghidoni, Luisa Benussi, Cristina Missale, PierFranco Spano, Arianna Bellucci
Loss-of-function mutations in the progranulin (PGRN) gene are a common cause of familial frontotemporal lobar degeneration (FTLD). This an age-related neurodegenerative disorder characterized by brain atrophy in the frontal and temporal lobes and with typical symptoms such as cognitive and memory impairment, profound behavioral abnormalities and personality changes, that are thought to be related to connectome dysfunctions. Recently, PGRN reduction has been found to induce a behavioural phenotype reminiscent of FTLD symptoms in mice by affecting neuron spine density and morphology, suggesting that the protein can influence neuronal structural plasticity...
September 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28899869/autism-like-behavior-caused-by-deletion-of-vaccinia-related-kinase-3-is-improved-by-trkb-stimulation
#19
Myung-Su Kang, Tae-Yong Choi, Hye Guk Ryu, Dohyun Lee, Seung-Hyun Lee, Se-Young Choi, Kyong-Tai Kim
Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory...
September 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28899819/information-content-of-dendritic-spines-after-motor-learning
#20
Davide Viggiano, Luisa Speranza, Marianna Crispino, Gian Carlo Bellenchi, Umberto di Porzio, Attilio Iemolo, Elvira De Leonibus, Floriana Volpicelli, Carla Perrone-Capano
Dendritic spines, small protrusions emerging from the dendrites of most excitatory synapses in the mammalian brain, are highly dynamic structures and their shape and number is continuously modulated by memory formation and other adaptive changes of the brain. In this study, using a behavioral paradigm of motor learning, we applied the non-linear analysis of dendritic spines to study spine complexity along dendrites of cortical and subcortical neural systems, such as the basal ganglia, that sustain important motor learning processes...
September 9, 2017: Behavioural Brain Research
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