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https://www.readbyqxmd.com/read/28542068/reduced-cortical-excitatory-synapse-number-in-apoe4-mice-is-associated-with-increased-calcineurin-activity
#1
Aidan L Neustadtl, Charisse N Winston, Maia Parsadanian, Bevan S Main, Sonia Villapol, Mark P Burns
Synaptic loss is a symptom of Alzheimer's disease (AD) that is associated with the onset of cognitive decline and the loss of executive function. The strongest genetic risk factor for AD is the APOE4 allele, which results in both a greater risk of developing AD as well as an earlier age of onset of AD. Dendritic spines, the anatomical substrate of the excitatory synapse, are reduced in the cortex of humanized APOE4 mice but the reason for this synaptic decline is unknown. Calcineurin, a calcium/calmodulin dependent phosphatase, is a mediator of dendritic spine retraction...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28522608/altered-learning-memory-and-social-behavior-in-type-1-taste-receptor-subunit-3-knockout-mice-is-associated-with-neuronal-dysfunction
#2
Bronwen Martin, Rui Wang, Wei-Na Cong, Caitlin M Daimon, Wells W Wu, Bin Ni, Kevin G Becker, Elin Lehrmann, William H Wood, Yongqing Zhang, Harmonie Etienne, Jaana van Gastel, Abdelkrim Azmi, Jonathan Janssens, Stuart Maudsley
The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor (GPCR) involved in sweet taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions, regulated by the sweet taste perception system, we hypothesized that a disruption of the sweet taste perception in the brain could have a key role in the development of cognitive dysfunction...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28521247/cognitive-performance-of-juvenile-monkeys-after-chronic-fluoxetine-treatment
#3
Mari S Golub, Edward P Hackett, Casey E Hogrefe, Csaba Leranth, John D Elsworth, Robert H Roth
Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention...
May 1, 2017: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/28516065/mir-142-5p-disrupts-neuronal-morphogenesis-underlying-porcine-hemagglutinating-encephalomyelitis-virus-infection-by-targeting-ulk1
#4
Zi Li, Yungang Lan, Kui Zhao, Xiaoling Lv, Ning Ding, Huijun Lu, Jing Zhang, Huiqing Yue, Junchao Shi, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central nervous system (CNS) and causes neurodegenerative disease in suckling piglets, but the understanding of its neuropathogenicity for neurological dysfunction remains limited. Here, we report that miR-142-5p is localized to neurons and negatively regulates neuronal morphogenesis in porcine hemagglutinating encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and dendrite formation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28510766/detection-of-3-3-dichlorobiphenyl-in-human-maternal-plasma-and-its-effects-on-axonal-and-dendritic-growth-in-primary-rat-neurons
#5
Sunjay Sethi, Kimberly P Keil, Hao Chen, Keri Hayakawa, Xueshu Li, Yanping Lin, Hans-Joachim Lehmler, Birgit Puschner, Pamela J Lein
3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is increasingly detected in environmental samples. While more highly chlorinated PCB congeners are known developmental neurotoxicants, nothing is known about the potential developmental neurotoxicity of PCB 11. To address this critical data gap, we measured PCB 11 levels in human maternal plasma and quantified the effects of PCB 11 and its major metabolites on morphometric parameters of neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of plasma from 241 pregnant women enrolled in the MARBLES study (University of California, Davis) detected PCB 11 in all samples at concentrations ranging from 0...
May 16, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28507508/improving-focal-photostimulation-of-cortical-neurons-with-pre-derived-wavefront-correction
#6
Julian M C Choy, Sharmila S Sané, Woei M Lee, Christian Stricker, Hans A Bachor, Vincent R Daria
Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions to the wavefront of the incoming light which broadens the focus and consequently reduces the intensity and degrades the resolution. Such effects are detrimental in techniques requiring focal stimulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28505229/oligodendrocyte-and-neuron-specific-nogo-a-restrict-dendritic-branching-and-spine-density-in-the-adult-mouse-motor-cortex
#7
Ajmal Zemmar, Chia-Chien Chen, Oliver Weinmann, Brigitt Kast, Flora Vajda, James Bozeman, Noel Isaad, Yi Zuo, Martin E Schwab
Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO)...
May 15, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28495333/sensory-experience-dependent-formation-of-perineuronal-nets-and-expression-of-cat-315-immunoreactive-components-in-the-mouse-somatosensory-cortex
#8
Hiroshi Ueno, Shunsuke Suemitsu, Motoi Okamoto, Yosuke Matsumoto, Takeshi Ishihara
Perineuronal nets (PNNs) are structures of extracellular matrix molecules surrounding the cell bodies and proximal dendrites of certain neurons. While PNNs are present throughout the mouse cerebral cortex, recent studies have shown that the components differ among cortical sub-regions and layers, suggesting region-specific functions. Parvalbumin-expressing interneurons (PV neurons) may be important regulators of cortical plasticity during the early "critical period" that is sensitive to sensory input. Here we examined the distribution and developmental functions of PNN components associated with PV neurons in the somatosensory cortex during the critical period...
May 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28488815/hypomorphic-conditional-deletion-of-e11-podoplanin-reveals-a-role-in-osteocyte-dendrite-elongation
#9
Katherine A Staines, Behzad Javaheri, Peter Hohenstein, Robert Fleming, Ekele Ikpegbu, Erin Unger, Mark Hopkinson, David J Buttle, Andrew A Pitsillides, Colin Farquharson
The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn(flox/flox) (cKO) mice and their Pdpn(flox/flox) controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (P < 0...
May 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28481348/cortical-gamma-band-synchronization-through-somatostatin-interneurons
#10
Julia Veit, Richard Hakim, Monika P Jadi, Terrence J Sejnowski, Hillel Adesnik
Gamma band rhythms may synchronize distributed cell assemblies to facilitate information transfer within and across brain areas, yet their underlying mechanisms remain hotly debated. Most circuit models postulate that soma-targeting parvalbumin-positive GABAergic neurons are the essential inhibitory neuron subtype necessary for gamma rhythms. Using cell-type-specific optogenetic manipulations in behaving animals, we show that dendrite-targeting somatostatin (SOM) interneurons are critical for a visually induced, context-dependent gamma rhythm in visual cortex...
May 8, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28473645/dopamine-receptors-differentially-control-binge-alcohol-drinking-mediated-synaptic-plasticity-of-the-core-nucleus-accumbens-direct-and-indirect-pathways
#11
Xincai Ji, Sucharita Saha, Jenya Kolpakova, Melissa Guildford, Andrew R Tapper, Gilles E Martin
Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intakes, is most prevalent in young adults and a risk factor for excessive alcohol consumption and alcohol dependence. Although alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking-in-the-dark (DID) as a model of binge alcohol drinking to assess its effects on spike-timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch clamp recordings with calcium imaging and optogenetics...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28463587/mild-traumatic-brain-injury-leads-to-decreased-inhibition-and-a-differential-response-of-calretinin-positive-interneurons-in-the-injured-cortex
#12
Mariana Brizuela, Catherine A Blizzard, Jyoti A Chuckowree, Kimberley A Pitman, Kaylene M Young, Tracey Dickson
It is clear that even mild forms of traumatic brain injury (TBI) can have lasting cognitive effects, however the specific cellular changes responsible for the functional deficits remain poorly understood. Previous studies suggest that not all neurons respond in the same way, and that changes to neuronal architecture may be subtype-specific. The current study aimed to characterize the response of interneurons to TBI. To model TBI in vitro, the neurites of primary cortical neurons were transected at 15 days in vitro...
May 2, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28461216/disruption-of-kv2-1-somato-dendritic-clusters-prevents-the-apoptogenic-increase-of-potassium-currents
#13
Jason A Justice, Anthony J Schulien, Kai He, Karen A Hartnett, Elias Aizenman, Niyathi H Shah
As the predominant mediator of the delayed rectifier current, KV2.1 is an important regulator of neuronal excitability. KV2.1, however, also plays a well-established role in apoptotic cell death. Apoptogenic stimuli induce syntaxin-dependent trafficking of KV2.1, resulting in an augmented delayed rectifier current that acts as a conduit for K(+) efflux required for pro-apoptotic protease/nuclease activation. Recent evidence suggests that KV2.1 somato-dendritic clusters regulate the formation of endoplasmic reticulum-plasma membrane junctions that function as scaffolding sites for plasma membrane trafficking of ion channels, including KV2...
April 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28458925/pathological-role-of-peptidyl-prolyl-isomerase-pin1-in-the-disruption-of-synaptic-plasticity-in-alzheimer-s-disease
#14
Lingyan Xu, Zhiyun Ren, Frances E Chow, Richard Tsai, Tongzheng Liu, Flavio Rizzolio, Silvia Boffo, Yungen Xu, Shaohui Huang, Carol F Lippa, Yuesong Gong
Synaptic loss is the structural basis for memory impairment in Alzheimer's disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28457820/differential-roles-for-akt-and-mtorc1-in-the-hypertrophy-of-pten-mutant-neurons-a-cellular-model-of-brain-overgrowth-disorders
#15
Ina Nikolaeva, Tatiana M Kazdoba, Beth Crowell, Gabriella D'Arcangelo
Mutations in the PI3K/Akt/mTOR signaling pathway or in the upstream negative regulator Pten cause human brain overgrowth disorders, such as focal cortical dysplasia and megalencephaly, and are characterized by the presence of hypertrophic neurons. These disorders often have a pediatric onset and a high comorbidity with drug-resistant epilepsy; however, effective pharmacological treatments are lacking. We established forebrain excitatory neuron-specific Pten-deficient cultures as an in vitro model of brain overgrowth disorders, and investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and neuronal growth...
April 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28453662/mglur5-tunes-ngf-trka-signaling-to-orient-spiny-stellate-neuron-dendrites-toward-thalamocortical-axons-during-whisker-barrel-map-formation
#16
Jui-Yen Huang, Hui-Chen Lu
Neurons receive and integrate synaptic inputs at their dendrites, thus dendritic patterning shapes neural connectivity and behavior. Aberrant dendritogenesis is present in neurodevelopmental disorders such as Down's syndrome and autism. Abnormal glutamatergic signaling has been observed in these diseases, as has dysfunction of the metabotropic glutamate receptor 5 (mGluR5). Deleting mGluR5 in cortical glutamatergic neurons disrupted their coordinated dendritic outgrowth toward thalamocortical axons and perturbed somatosensory circuits...
April 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28450828/spine-enlargement-of-pyramidal-tract-type-neurons-in-the-motor-cortex-of-a-rat-model-of-levodopa-induced-dyskinesia
#17
Tatsuya Ueno, Haruo Nishijima, Shinya Ueno, Masahiko Tomiyama
Growing evidence suggests that abnormal synaptic plasticity of cortical neurons underlies levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). Spine morphology reflects synaptic plasticity resulting from glutamatergic transmission. We previously reported that enlargement of the dendritic spines of intratelencephalic-type (IT) neurons in the primary motor cortex (M1) is linked to the development of LID. However, the relevance of another M1 neuron type, pyramidal-tract (PT) neurons, to LID remains unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28445771/cyclin-dependent-kinase-5-collapsin-response-mediator-protein-2-pathway-may-mediate-sevoflurane-induced-dendritic-development-abnormalities-in-rat-cortical-neurons
#18
Yafang Liu, Daowei Lin, Chuiliang Liu, Yifan Zhao, Zhiwen Shen, Kun Zhang, Minghui Cao, Yujuan Li
Sevoflurane has been reported to induce neurotoxicity and cognitive impairment in the developing brains. However, the underlying molecular mechanisms remain poorly understood. Recent studies have demonstrated aberrant cyclin-dependent kinase 5 (CDK5) activity is implicated in inhaled anesthetic-induced neurotoxicity. CDK5/CRMP2 signaling is involved in the cortical and hippocampal dendritic development. The aim of present study is to investigate whether the CDK5/CRMP2 pathway mediates sevoflurane-induced dendritic development abnormalities...
April 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28438110/temporal-progression-of-lesions-in-guinea-pigs-infected-with-lassa-virus
#19
T M Bell, C I Shaia, J J Bearss, M E Mattix, K A Koistinen, S P Honnold, X Zeng, C D Blancett, G C Donnelly, J D Shamblin, E R Wilkinson, K A Cashman
Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28428560/combination-of-high-density-microelectrode-array-and-patch-clamp-recordings-to-enable-studies-of-multisynaptic-integration
#20
David Jäckel, Douglas J Bakkum, Thomas L Russell, Jan Müller, Milos Radivojevic, Urs Frey, Felix Franke, Andreas Hierlemann
We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration...
April 20, 2017: Scientific Reports
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