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Dendritic spine

Nancy R Stallings, Melissa A O'Neal, Jie Hu, Ege T Kavalali, Ilya Bezprozvanny, James S Malter
Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that dendritic spine loss is induced by soluble, multimeric amyloid-β (Aβ42 ), which, through postsynaptic signaling, activates the protein phosphatase calcineurin. We investigated how calcineurin caused spine pathology and found that the cis-trans prolyl isomerase Pin1 was a critical downstream target of Aβ42 -calcineurin signaling...
March 20, 2018: Science Signaling
Ryusuke Koshida, Saki Tome, Yosuke Takei
Dendritic spines, the postsynaptic compartments at excitatory synapses, are capable of changing their shape and size to modulate synaptic transmission. The actin cytoskeleton and a variety of actin-binding proteins play a critical role in the dynamics of dendritic spines. Class I myosins are monomeric motor proteins that move along actin filaments using the energy of ATP hydrolysis. Of these class I myosins, myosin Id, the mammalian homolog of Drosophila Myo31DF, has been reported to be expressed in neurons, whereas its subcellular localization in neurons remained unknown...
March 17, 2018: Experimental Cell Research
Hitoshi Okazawa
Tau phosphorylation has come into the limelight again, this time as a critical player in the earliest stages of dementia pathology. Mislocalization of phosphorylated tau to dendritic spines and the resultant degeneration of synapses are observed across multiple neurodegenerative diseases, even in the absence of tau aggregation. Moreover, other molecules phosphorylated by the same kinases, such as MARCKS, might contribute to ultra-early phase pathology by promoting synapse dysfunction.
March 20, 2018: ACS Chemical Neuroscience
Erica C Dresselhaus, Matthew C H Boersma, Mollie K Meffert
Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor kappa B (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine-enrichment (ΔSEp65) but retains inherent transcriptional activity equivalent to wild-type p65...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daniel M Vahaba, Luke Remage-Healey
Steroid hormones, such as estrogens, were once thought to be exclusively synthesized in the ovaries and enact transcriptional changes over the course of hours to days. However, estrogens are also locally synthesized within neural circuits, wherein they rapidly (within minutes) modulate a range of behaviors, including spatial cognition and communication. Here, we review the role of brain-derived estrogens (neuroestrogens) as modulators within sensory circuits in songbirds. We first present songbirds as an attractive model to explore how neuroestrogens in auditory cortex modulate vocal communication processing and learning...
March 16, 2018: Hormones and Behavior
Valerie Jeanneret, Juan P Ospina, Ariel Diaz, Luis G Manrique, Paola Merino, Laura Gutierrez, Enrique Torre, Fang Wu, Lihong Cheng, Manuel Yepes
Cerebral ischemia causes the presynaptic release of tissue-type plasminogen activator (tPA). The postsynaptic density (PSD) is a postsynaptic structure that provides a matrix where signaling transduction of excitatory synapses takes place. The postsynaptic density protein-95 (PSD-95) is the most abundant scaffolding protein in the postsynaptic density (PSD), where it modulates the postsynaptic response to the presynaptic release of glutamate by regulating the anchoring of glutamate receptors to the PSD. We found that tPA induces the local translation of PSD-95 mRNA and the subsequent recruitment of PSD-95 protein to the PSD, via plasminogen-independent activation of TrkB receptors...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Hei Ming Lai, Alan King Lun Liu, Harry Ho Man Ng, Marc H Goldfinger, Tsz Wing Chau, John DeFelice, Bension S Tilley, Wai Man Wong, Wutian Wu, Steve M Gentleman
Modern clearing techniques for the three-dimensional (3D) visualisation of neural tissue microstructure have been very effective when used on rodent brain but very few studies have utilised them on human brain material, mainly due to the inherent difficulties in processing post-mortem tissue. Here we develop a tissue clearing solution, OPTIClear, optimised for fresh and archival human brain tissue, including formalin-fixed paraffin-embedded material. In light of practical challenges with immunostaining in tissue clearing, we adapt the use of cresyl violet for visualisation of neurons in cleared tissue, with the potential for 3D quantification in regions of interest...
March 14, 2018: Nature Communications
Krzysztof Kucharz, Martin Lauritzen
Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity...
March 12, 2018: Brain: a Journal of Neurology
Eliseo Portilla-de Buen, Hermelinda Salgado-Ceballos, David González-Tapia, Caridad Leal-Cortés, Rodrigo Mondragón-Lozano, Stephanie Sánchez-Torres, Laura Álvarez-Mejía, Omar Fabela-Sánchez, Néstor I Martínez-Torres, Myrna M González-Ramírez, Nallely Vázquez-Hernández, Ignacio González-Burgos
BACKGROUND: Spinal cord injury (SCI) is highly incapacitating, and the neurobiological factors involved in an eventual functional recovery remain uncertain. Plastic changes to dendritic spines are closely related with the functional modifications of behavior. AIM OF THE STUDY: To explore the plastic response of dendritic spines in motoneurons after SCI. METHODS: Female rats were assigned to either of three groups: Intact (no manipulations), Sham (T9 laminectomy), and SCI (T9 laminectomy and spinal cord contusion)...
March 10, 2018: Archives of Medical Research
Mana Ogawa, Toshitada Nagai, Yoshikazu Saito, Hitonari Miyaguchi, Kei Kumakura, Keiko Abe, Tomiko Asakura
Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis...
March 7, 2018: Biochemical and Biophysical Research Communications
Kenji Hanamura, Yousuke Kamata, Hiroyuki Yamazaki, Nobuhiko Kojima, Tomoaki Shirao
Dendritic spines have stable filamentous actin (F-actin) and dynamic F-actin. The formation of stable F-actin plays a pivotal role in spine formation. Drebrin binds to and stabilizes F-actin in dendritic spines. Interestingly, the conversion of the drebrin E isoform to drebrin A occurs in parallel with synapse formation, suggesting that this conversion promotes synapse formation via F-actin accumulation. In this study, we measured the dynamics of GFP-tagged drebrin E (GFP-DE) and drebrin A (GFP-DA) in cultured hippocampal neurons by fluorescence recovery after photobleaching analysis...
March 6, 2018: Neuroscience
Zhi-Fang Deng, Hui-Ling Zheng, Jian-Guo Chen, Yi Luo, Jun-Feng Xu, Gang Zhao, Jia-Jing Lu, Hou-Hong Li, Shuang-Qi Gao, Deng-Zheng Zhang, Ling-Qiang Zhu, Yong-Hui Zhang, Fang Wang
β-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of β-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons...
March 7, 2018: Cerebral Cortex
Lifu Sheng, Iryna Leshchyns'ka, Vladimir Sytnyk
The neural cell adhesion molecule 2 (NCAM2) is encoded by a gene on chromosome 21 in humans. NCAM2 accumulates in synapses, but its role in regulation of synapse formation remains poorly understood. We demonstrate that an increase in NCAM2 levels results in increased instability of dendritic protrusions and reduced conversion of protrusions to dendritic spines in mouse cortical neurons. NCAM2 overexpression induces an increase in the frequency of submembrane Ca2+ spikes localized in individual dendritic protrusions and promotes propagation of submembrane Ca2+ spikes over segments of dendrites or the whole dendritic tree...
March 7, 2018: Cerebral Cortex
Andrew Coleman, Thomas Biederer
In this issue of Neuron, Mikhaylova et al. (2018) report how the Ca2+ sensor caldendrin interacts in dendritic spines with cortactin to control actin remodeling. Combining molecular and functional approaches, this work gains insights into postsynaptic dynamics relevant for synaptic plasticity.
March 7, 2018: Neuron
M Martinez-Morga, M P Quesada-Rico, C Bueno, S Martinez
AIM: To know the neural processes linked to the activity of brain circuits in order to understand the consequences of their dysfunction and their role in the development of neurodevelopmental diseases, such as autistic spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). DEVELOPMENT: The activity of neuronal circuits is the neurobiological basis of behavior and mental activity (emotions, memory and thoughts). The processes of differentiation of neural cells and the formation of circuits by synaptic contacts between neurons (synaptogenesis) occur in the central nervous system during the late stages of prenatal development and the first months after birth...
March 1, 2018: Revista de Neurologia
Masayoshi Kurachi, Tsutomu Takahashi, Tomiki Sumiyoshi, Takashi Uehara, Michio Suzuki
Background: A recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome...
2018: Frontiers in Psychiatry
Chia-Sheng Pai, Pranao K Sharma, Hsien-Ting Huang, Srivaishnavi Loganathan, Heng Lin, Yu-Luan Hsu, Sarayut Phasuk, Ingrid Y Liu
The genetic and molecular basis underlying fear memory formation is a key theme in anxiety disorder research. Because activating transcription factor 3 ( ATF3 ) is induced under stress conditions and is highly expressed in the hippocampus, we hypothesize that ATF3 plays a role in fear memory formation. We used fear conditioning and various other paradigms to test Atf3 knockout mice and study the role of ATF3 in processing fear memory. The results demonstrated that the lack of ATF3 specifically enhanced the expression of fear memory, which was indicated by a higher incidence of the freeze response after fear conditioning, whereas the occurrence of spatial memory including Morris Water Maze and radial arm maze remained unchanged...
2018: Frontiers in Molecular Neuroscience
Fenghua Chen, Jibrin Danladi, Maryam Ardalan, Betina Elfving, Heidi K Müller, Gregers Wegener, Connie Sanchez, Jens R Nyengaard
Background: Preclinical studies have indicated that antidepressant effect of vortioxetine involves increased synaptic plasticity and promotion of spine maturation. Mitochondria dysfunction may contribute to the pathophysiological basis of major depressive disorder. Taking into consideration that vortioxetine increases spine number and dendritic branching in hippocampus CA1 faster than fluoxetine, we hypothesize that new spines induced by vortioxetine can rapidly form functional synapses by mitochondrial support, accompanied by increased brain-derived neurotrophic factor (BDNF)-signaling...
March 5, 2018: International Journal of Neuropsychopharmacology
Kazuaki Sawada, Ryosuke Kawakami, Ryuichi Shigemoto, Tomomi Nemoto
Three-dimensional (3D) super-resolution microscopy technique structured illumination microscopy (SIM) imaging of dendritic spines along the dendrite has not been previously performed in fixed tissues, mainly due to deterioration of the stripe pattern of the excitation laser induced by light scattering and optical aberrations. To address this issue and solve these optical problems, we applied a novel clearing reagent, LUCID, to fixed brains. In SIM imaging, the penetration depth and the spatial resolution were improved in LUCID-treated slices, and 160-nm spatial resolution was obtained in a large portion of the imaging volume on a single apical dendrite...
March 7, 2018: European Journal of Neuroscience
Monique Richter, María Luciana Negro-Demontel, Daniela Blanco-Ocampo, Eliseo Taranto, Natalia Lago, Hugo Peluffo
Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long-term follow-up is needed. We have used the Thy1-YFP-H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury...
February 21, 2018: Current Protocols in Immunology
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