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https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#1
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid beta-peptide (Abeta) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Abeta plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28922832/fast-spiking-parvalbumin-interneurons-are-frequently-myelinated-in-the-cerebral-cortex-of-mice-and-humans
#2
J Stedehouder, J J Couey, D Brizee, B Hosseini, J A Slotman, C M F Dirven, G Shpak, A B Houtsmuller, S A Kushner
Myelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination of GABAergic interneurons in the cerebral cortex. Here, we report that a large fraction of myelin in mouse cerebral cortex ensheaths GABAergic interneurons, reaching up to 80% in hippocampal subregions. Moreover, we find that a very high proportion of neocortical and hippocampal parvalbumin (PV) interneurons exhibit axonal myelination...
October 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28913875/alterations-in-the-%C3%AE-2-%C3%AE-ligand-thrombospondin-1-in-a-rat-model-of-spontaneous-absence-epilepsy-and-in-patients-with-idiopathic-genetic-generalized-epilepsies
#3
Ines Santolini, Roberta Celli, Milena Cannella, Tiziana Imbriglio, Michela Guiducci, Pasquale Parisi, Julian Schubert, Michele Iacomino, Federico Zara, Holger Lerche, Slavianka Moyanova, Richard Teke Ngomba, Gilles van Luijtelaar, Giuseppe Battaglia, Valeria Bruno, Pasquale Striano, Ferdinando Nicoletti
OBJECTIVES: Thrombospondins, which are known to interact with the α2 δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs)...
September 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28912692/calsyntenins-are-expressed-in-a-dynamic-and-partially-overlapping-manner-during-neural-development
#4
Gemma de Ramon Francàs, Tobias Alther, Esther T Stoeckli
Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1) was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28912273/neuroligin-4-regulates-synaptic-growth-via-the-bone-morphogenetic-protein-bmp-signaling-pathway-at-the-drosophila-neuromuscular-junction
#5
Xinwang Zhang, Menglong Rui, Guangmin Gan, Cong Huang, Jukang Yi, Huihui Lv, Wei Xie
The neuroligin (Nlg) family of neural cell adhesion molecules is thought to be required for synapse formation and development, and has been linked to the development of autism spectrum disorders in humans. In Drosophila melanogaster, mutations in the neuroligin 1-3 genes have been reported to induce synapse developmental defects at neuromuscular junctions (NMJs), but the role of neuroligin 4 (dnlg4) in synapse development has not been determined. Here, we report that the Drosophila neuroligin 4 (DNlg4) is different from DNlg1-3 that it presynaptically regulates NMJ synapse development...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28901288/multiple-conserved-cell-adhesion-protein-interactions-mediate-neural-wiring-of-a-sensory-circuit-in-c-elegans
#6
Byunghyuk Kim, Scott W Emmons
Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG...
September 13, 2017: ELife
https://www.readbyqxmd.com/read/28899819/information-content-of-dendritic-spines-after-motor-learning
#7
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
https://www.readbyqxmd.com/read/28894610/maturation-refinement-and-serotonergic-modulation-of-cerebellar-cortical-circuits-in-normal-development-and-in-murine-models-of-autism
#8
REVIEW
Eriola Hoxha, Pellegrino Lippiello, Bibiana Scelfo, Filippo Tempia, Mirella Ghirardi, Maria Concetta Miniaci
The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28892038/measuring-synaptic-vesicle-endocytosis-in-cultured-hippocampal-neurons
#9
Seth Villarreal, Sung Hoon Lee, Ling-Gang Wu
During endocytosis, fused synaptic vesicles are retrieved at nerve terminals, allowing for vesicle recycling and thus the maintenance of synaptic transmission during repetitive nerve firing. Impaired endocytosis in pathological conditions leads to decreases in synaptic strength and brain functions. Here, we describe methods used to measure synaptic vesicle endocytosis at the mammalian hippocampal synapse in neuronal culture. We monitored synaptic vesicle protein endocytosis by fusing a synaptic vesicular membrane protein, including synaptophysin and VAMP2/synaptobrevin, at the vesicular lumenal side, with pHluorin, a pH-sensitive green fluorescent protein that increases its fluorescence intensity as the pH increases...
September 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28891515/a-computational-approach-towards-the-microscale-mouse-brain-connectome-from-the-mesoscale
#10
Tielin Zhang, Yi Zeng, Bo Xu
The wiring diagram of the mouse brain presents an indispensable foundation for the research on basic and applied neurobiology. It is also essential as a structural foundation for computational simulation of the brain. Different scales of the connectome give us different hints and clues to understand the functions of the nervous system and how they process information. However, compared to the macroscale and most recent mesoscale mouse brain connectome studies, there is no complete whole brain microscale connectome available because of the scalability and accuracy of automatic recognition techniques...
2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28890419/arc-protein-a-flexible-hub-for-synaptic-plasticity-and-cognition
#11
REVIEW
Oleksii Nikolaienko, Sudarshan Patil, Maria Steene Eriksen, Clive R Bramham
Mammalian excitatory synapses express diverse types of synaptic plasticity. A major challenge in neuroscience is to understand how a neuron utilizes different types of plasticity to sculpt brain development, function, and behavior. Neuronal activity-induced expression of the immediate early protein, Arc, is critical for long-term potentiation and depression of synaptic transmission, homeostatic synaptic scaling, and adaptive functions such as long-term memory formation. However, the molecular basis of Arc protein function as a regulator of synaptic plasticity and cognition remains a puzzle...
September 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28888867/pick1facilitates-lasting-reduction-in-glua2-concentration-in-the-hippocampus-during-chronic-epilepsy
#12
Jan-Øyvind Lorgen, Daniel Lawer Egbenya, Janniche Hammer, Svend Davanger
Overstimulation of glutamate receptors resulting in excessive intracellular calcium concentrations is a major cause of neuronal cell death in epilepsy. The main source of increased calcium concentration during this excitotoxicity is an influx through NMDA subtype of glutamate receptors. The GluR2 hypothesis states that following a neurological insult such as an epileptic seizure, the AMPAR subunit GluR2 protein is down regulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPARs which might further enhance the toxicity of the neurotransmitter, glutamate...
August 31, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28887651/a-cell-culture-model-for-investigation-of-synapse-influenceability-epigenetics-expression-and-function-of-gene-targets-important-for-synapse-formation-and-preservation-in-sh-sy5y-neuroblastoma-cells-differentiated-by-retinoic-acid
#13
Kirsten Jahn, C Wieltsch, N Blumer, M Mehlich, H Pathak, A Q Khan, H Hildebrandt, H Frieling
SH-SY5Y neuroblastoma cells are frequently used for different neuronal cell culture models. As there is no "gold-standard", miscellaneous protocols exist to differentiate these cells into a neuronal cell type. Here, the aim was to find a differentiation condition making cells suitable for investigation of influenceability of synapses by environmental conditions in pharmacologic experiments. For this purpose, effects on synapse molecules should be somehow rateable and cells should be usable for functional analysis like calcium imaging...
September 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28885486/bacopa-monnieri-extract-enhances-learning-dependent-hippocampal-long-term-synaptic-potentiation
#14
Charkriya Promsuban, Suveerawan Limsuvan, Pravit Akarasereenont, Kanokwan Tilokskulchai, Sompol Tapechum, Narawut Pakaprot
Bacopa monnieri has been used in Ayurvedic medicine as a memory enhancer for a long time; however, its direct effect on synaptic plasticity has not been investigated. To the best of our knowledge, this study is the first to report the effect of B. monnieri on long-term synaptic potentiation in acute hippocampal slices. Adult male Wistar rats were orally administered either sterile water or the ethanolic extract of B. monnieri for 60 days. The extracellular recording was performed to measure the field excitatory postsynaptic potential in the acute hippocampal slices of these rats...
September 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/28884027/aav-klf7-promotes-descending-propriospinal-neuron-axonal-plasticity-after-spinal-cord-injury
#15
Wen-Yuan Li, Ying Wang, Feng-Guo Zhai, Ping Sun, Yong-Xia Cheng, Ling-Xiao Deng, Zhen-Yu Wang
DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28882305/methods-related-to-studying-tau-fragmentation
#16
Adriana Ferreira, Sana Afreen
Several tau posttranslational modifications have been implicated in neuronal degeneration. Among them, tau fragmentation has been identified not only in brain samples obtained from Alzheimer's disease (AD) and related disorder subjects but also in AD culture and animal models. Some of these tau fragments have not been extensively studied. In contrast, data obtained recently showed that tau fragmentation mediated by enhanced or abnormal calpain, caspase 2, caspase 3, and asparagine endopeptidase activity results in the formation of toxic fragments...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28878628/early-correlated-network-activity-in-the-hippocampus-its-putative-role-in-shaping-neuronal-circuits
#17
REVIEW
Marilena Griguoli, Enrico Cherubini
Synchronized neuronal activity occurring at different developmental stages in various brain structures represents a hallmark of developmental circuits. This activity, which differs in its specific patterns among animal species may play a crucial role in de novo formation and in shaping neuronal networks. In the rodent hippocampus in vitro, the so-called giant depolarizing potentials (GDPs) constitute a primordial form of neuronal synchrony preceding more organized forms of activity such as oscillations in the theta and gamma frequency range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28874186/age-dependent-changes-in-synaptic-plasticity-enhance-tau-oligomerization-in-the-mouse-hippocampus
#18
Tetsuya Kimura, Mamiko Suzuki, Takumi Akagi
The aggregation mechanism of phosphorylated tau is an important therapeutic target for tauopathies, including Alzheimer's disease, although the mechanism by which aggregation occurs is still unknown. Because the phosphorylation process of tau is involved in the trafficking of AMPA receptors, which accompanies the long-term depression (LTD) of synapses, we examined the effect of LTD-inducing low-frequency stimulation (LFS) on the formation of pathological tau aggregates in adult and aged wild-type mice. Our biochemical analysis demonstrated that LFS led to the formation of sarkosyl-insoluble (SI) tau oligomers in aged hippocampi but not in adult hippocampi in wild-type mice...
September 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28872625/salivary-gland-derived-bdnf-overexpression-in-mice-exerts-an-anxiolytic-effect
#19
Juri Saruta, Masahiro To, Masahiro Sugimoto, Yuko Yamamoto, Tomoko Shimizu, Yusuke Nakagawa, Hiroko Inoue, Ichiro Saito, Keiichi Tsukinoki
Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemagglutinin (HA)-tagged mouse Bdnf cDNA) to specifically express BDNF in mouse salivary glands...
September 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28871958/control-of-ampa-receptor-activity-by-the-extracellular-loops-of-auxiliary-proteins
#20
Irene Riva, Clarissa Eibl, Rudolf Volkmer, Anna L Carbone, Andrew Jr Plested
At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including TARPs. However, how TARPs modulate AMPA receptor gating remains poorly understood. We built structural models of TARP-AMPA receptor complexes for TARPs γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of TARPs. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly...
August 30, 2017: ELife
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