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https://www.readbyqxmd.com/read/28636962/reactive-astrocytes-production-function-and-therapeutic-potential
#1
REVIEW
Shane A Liddelow, Ben A Barres
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636662/differential-regulation-of-polarized-synaptic-vesicle-trafficking-and-synapse-stability-in-neural-circuit-rewiring-in-caenorhabditis-elegans
#2
Naina Kurup, Dong Yan, Karina Kono, Yishi Jin
Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28631008/regulation-of-neural-circuit-formation-by-protocadherins
#3
REVIEW
Stacey L Peek, Kar Men Mah, Joshua A Weiner
The protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990s. Data implicating the Pcdhs, including ~60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ~10 non-clustered Pcdhs, in the regulation of neural development have continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination...
June 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28628896/cholinergic-neuron-gene-expression-differences-captured-by-translational-profiling-in-a-mouse-model-of-alzheimer-s-disease
#4
Paul M McKeever, TaeHyung Kim, Andrew R Hesketh, Laura MacNair, Denise Miletic, Giorgio Favrin, Stephen G Oliver, Zhaolei Zhang, Peter St George-Hyslop, Janice Robertson
Cholinergic neurotransmission is impaired in Alzheimer's disease (AD), and loss of basal forebrain cholinergic neurons is a key component of disease pathogenicity and symptomatology. To explore the molecular basis of this cholinergic dysfunction, we paired translating ribosome affinity purification (TRAP) with RNA sequencing (TRAP-Seq) to identify the actively translating mRNAs in anterior forebrain cholinergic neurons in the TgCRND8 mouse model of AD. Bioinformatic analyses revealed the downregulation of 67 of 71 known cholinergic-related transcripts, consistent with cholinergic neuron dysfunction in TgCRND8 mice, as well as transcripts related to oxidative phosphorylation, neurotrophins, and ribosomal processing...
May 25, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28625682/are-circadian-rhythms-new-pathways-to-understand-autism-spectrum-disorder
#5
M-M Geoffray, A Nicolas, M Speranza, N Georgieff
Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep- wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin...
June 15, 2017: Journal of Physiology, Paris
https://www.readbyqxmd.com/read/28625569/synaptic-dysfunction-in-alzheimer-s-disease-from-the-role-of-amyloid-%C3%AE-peptide-to-the-%C3%AE-secretase-adam10
#6
Stefano Musardo, Elena Marcello
Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on patients, caregivers and society, it represents the largest unmet medical need in neurology, because it is currently incurable. In the last few years, the amyloid hypothesis, which points to amyloid β-peptide (Aβ) as the initiating factor in AD, had a central role in the development of therapeutic strategies for AD...
June 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28625420/formation-and-remodeling-of-the-brain-extracellular-matrix-in-neural-plasticity-roles-of-chondroitin-sulfate-and-hyaluronan
#7
REVIEW
Shinji Miyata, Hiroshi Kitagawa
BACKGROUND: The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624530/the-emerging-role-of-wnt-signaling-dysregulation-in-the-understanding-and-modification-of-age-associated-diseases
#8
REVIEW
Lizbeth García-Velázquez, Clorinda Arias
Wnt signaling is a highly conserved pathway that participates in multiple aspects of cellular function during development and in adults. In particular, this pathway has been implicated in cell fate determination, proliferation and cell polarity establishment. In the brain, it contributes to synapse formation, axonal remodeling, dendrite outgrowth, synaptic activity, neurogenesis and behavioral plasticity. The expression and distribution of Wnt components in different organs vary with age, which may have important implications for preserving tissue homeostasis...
June 14, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28621929/kinetic-analysis-reveals-the-identity-of-a%C3%AE-metal-complex-responsible-for-the-initial-aggregation-of-a%C3%AE-in-the-synapse
#9
Thomas Branch, Mauricio Barahona, Charlotte A Dodson, Liming Ying
The mechanism of Aβ aggregation in the absence of metal ions is well established, yet the role that Zn(2+) and Cu(2+), the two most studied metal ions, released during neurotransmission, play in promoting Aβ aggregation in the vicinity of neuronal synapses remains elusive. Here we report the kinetics of Zn(2+) binding to Aβ and Zn(2+)/Cu(2+) binding to Aβ-Cu to form ternary complexes under near physiological conditions (nM Aβ, µM metal ions). We find that these reactions are several orders of magnitude slower than Cu(2+) binding to Aβ...
June 16, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28615657/bone-morphogenetic-protein-4-promotes-the-survival-and-preserves-the-structure-of-flow-sorted-bhlhb5-cochlear-spiral-ganglion-neurons-in-vitro
#10
Muhammad Waqas, Shan Sun, Chuanyin Xuan, Qiaojun Fang, Xiaoli Zhang, Irum-Us Islam, Jieyu Qi, Shasha Zhang, Xia Gao, Mingliang Tang, Haibo Shi, Huawei Li, Renjie Chai
SGNs are the primary auditory neurons, and damage or loss of SGNs leads to sensorineural hearing loss. BMP4 is a growth factor that belongs to the TGF-β superfamily and has been shown to play a key role during development, but little is known about its effect on postnatal cochlear SGNs in mice. In this study, we used the P3 Bhlhb5-cre/tdTomato transgenic mouse model and FACS to isolate a pure population of Bhlhb5+ SGNs. We found that BMP4 significantly promoted SGN survival after 7 days of culture. We observed fewer apoptotic cells and decreased expression of pro-apoptotic marker genes after BMP4 treatment...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614919/-effects-of-developmental-exposure-to-dehp-on-learning-and-memory-of-mice
#11
D J Wu, B B Luo, Q W Feng, Q N Wang
Objective: To investigate the effects of developmental exposure to DEHP on learning and memory of mice. Methods: Male littermates of ICR mice randomly assigned to five experimental groups (n=14 for each condition) on PND4 to receive distilled water, vehicle and 10, 50 and 200 mg/ (kg·d) DEHP from PND5 to PND38 by gavage, weighing and recording body weight of mice. Open field task were conducted on PND 26 and Morris water maze task were begun from PND30 to PND 37 to evaluate spontaneous exploration activity and emotion, spatial learning and memory performance of pubertal mice, respectively...
April 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28611607/generating-executable-models-of-the-drosophila-central-complex
#12
Lev E Givon, Aurel A Lazar, Chung-Heng Yeh
The central complex (CX) is a set of neuropils in the center of the fly brain that have been implicated as playing an important role in vision-mediated behavior and integration of spatial information with locomotor control. In contrast to currently available data regarding the neural circuitry of neuropils in the fly's vision and olfactory systems, comparable data for the CX neuropils is relatively incomplete; many categories of neurons remain only partly characterized, and the synaptic connectivity between CX neurons has yet to be fully determined...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28611576/maternal-different-degrees-of-iodine-deficiency-during-pregnant-and-lactation-impair-the-development-of-cerebellar-pinceau-in-offspring
#13
Jing Dong, Heling Song, Yuan Wang, Min Li, Ye Yu, Yi Wang, Jie Chen
Aims: Iodine is critical for synthesis of thyroid hormones (TH). And iodine deficiency (ID) is one of the most significant reasons of intellectual disability and motor memory impairment, although the potential mechanisms are still under investigation. Presently, mild ID and marginal ID are largely ignored problems for women of child bearing age. Mild ID is a subtle form of TH deficiency, which shows low levels of free thyroxine (FT4) and relatively normal free triiodothyronine (FT3) or thyroid stimulation hormone (TSH)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28607047/numbers-of-presynaptic-ca-2-channel-clusters-match-those-of-functionally-defined-vesicular-docking-sites-in-single-central-synapses
#14
Takafumi Miki, Walter A Kaufmann, Gerardo Malagon, Laura Gomez, Katsuhiko Tabuchi, Masahiko Watanabe, Ryuichi Shigemoto, Alain Marty
Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such "simple synapses" indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28607044/regulation-of-spinogenesis-in-mature-purkinje-cells-via-mglur-pkc-mediated-phosphorylation-of-camkii%C3%AE
#15
Takeyuki Sugawara, Chihiro Hisatsune, Hiroyuki Miyamoto, Naoko Ogawa, Katsuhiko Mikoshiba
Dendritic spines of Purkinje cells form excitatory synapses with parallel fiber terminals, which are the primary sites for cerebellar synaptic plasticity. Nevertheless, how density and morphology of these spines are properly maintained in mature Purkinje cells is not well understood. Here we show an activity-dependent mechanism that represses excessive spine development in mature Purkinje cells. We found that CaMKIIβ promotes spine formation and elongation in Purkinje cells through its F-actin bundling activity...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28605376/anatomically-inspired-three-dimensional-micro-tissue-engineered-neural-networks-for-nervous-system-reconstruction-modulation-and-modeling
#16
Laura A Struzyna, Dayo O Adewole, Wisberty J Gordián-Vélez, Michael R Grovola, Justin C Burrell, Kritika S Katiyar, Dmitriy Petrov, James P Harris, D Kacy Cullen
Functional recovery rarely occurs following injury or disease-induced degeneration within the central nervous system (CNS) due to the inhibitory environment and the limited capacity for neurogenesis. We are developing a strategy to simultaneously address neuronal and axonal pathway loss within the damaged CNS. This manuscript presents the fabrication protocol for micro-tissue engineered neural networks (micro-TENNs), implantable constructs consisting of neurons and aligned axonal tracts spanning the extracellular matrix (ECM) lumen of a preformed hydrogel cylinder hundreds of microns in diameter that may extend centimeters in length...
May 31, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28600320/limited-distal-organelles-and-synaptic-function-in-extensive-monoaminergic-innervation
#17
Juan Tao, Dinara Bulgari, David L Deitcher, Edwin S Levitan
Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with volume transmission and neuromodulation by monoamines and neuropeptides and mammalian dopamine neuron vulnerability. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28599119/dendrites-enable-a-robust-mechanism-for-neuronal-stimulus-selectivity
#18
Romain D Cazé, Sarah Jarvis, Amanda J Foust, Simon R Schultz
Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli...
June 9, 2017: Neural Computation
https://www.readbyqxmd.com/read/28598851/mitochondrial-dysfunction-triggers-synaptic-deficits-via-activation-of-p38-map-kinase-signaling-in-differentiated-alzheimer-s-disease-trans-mitochondrial-cybrid-cells
#19
Qing Yu, Fang Du, Justin T Douglas, Haiyang Yu, Shirley ShiDu Yan, Shi Fang Yan
Loss of synapse and synaptic dysfunction contribute importantly to cognitive impairment in Alzheimer's disease (AD). Mitochondrial dysfunction and oxidative stress are early pathological features in AD-affected brain. However, the effect of AD mitochondria on synaptogenesis remains to be determined. Using human trans-mitochondrial "cybrid" (cytoplasmic hybrid) neuronal cells whose mitochondria were transferred from platelets of patients with sporadic AD or age-matched non-AD subjects with relatively normal cognition, we provide the first evidence of mitochondrial dysfunction compromises synaptic development and formation of synapse in AD cybrid cells in response to chemical-induced neuronal differentiation...
June 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28591617/neuronal-activity-regulated-alternative-mrna-splicing
#20
Guido Hermey, Nils Blüthgen, Dietmar Kuhl
Activity-regulated gene transcription underlies plasticity-dependent changes in the molecular composition and structure of neurons. Numerous genes whose expression is induced by different neuronal plasticity inducing pathways have been identified, but the alteration of gene expression levels represents only part of the complexity of the activity-regulated transcriptional program. Alternative splicing of precursor mRNA is an additional mechanism that modulates the activity-dependent transcriptional signature...
June 4, 2017: International Journal of Biochemistry & Cell Biology
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