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https://www.readbyqxmd.com/read/28335379/the-role-of-adenosine-signaling-in-headache-a-review
#1
REVIEW
Nathan T Fried, Melanie B Elliott, Michael L Oshinsky
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments...
March 13, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28334897/genetic-absence-of-alox5-protects-from-homocysteine-induced-memory-impairment-tau-phosphorylation-and-synaptic-pathology
#2
Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò
Elevated level of homocysteine (Hcy) is considered a risk factor for neurodegenerative diseases, but the mechanisms remain to be established. Since high Hcy is associated with an up-regulation of the ALOX5 gene product, the 5Lipoxygenase (5LO), herein we investigated whether this activation is responsible for the Hcy effect on neurodegeneration or is a secondary event.To reach this goal, wild type mice and mice genetically deficient for 5LO were assessed after being exposed to a diet known to significantly increase brain levels of Hcy...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334879/altered-sleep-homeostasis-correlates-with-cognitive-impairment-in-patients-with-focal-epilepsy
#3
Melanie Boly, Benjamin Jones, Graham Findlay, Erin Plumley, Armand Mensen, Bruce Hermann, Guilio Tononi, Rama Maganti
In animal studies, both seizures and interictal spikes induce synaptic potentiation. Recent evidence suggests that electroencephalogram slow wave activity during sleep reflects synaptic potentiation during wake, and that its homeostatic decrease during the night is associated with synaptic renormalization and its beneficial effects. Here we asked whether epileptic activity induces plastic changes that can be revealed by high-density electroencephalography recordings during sleep in 15 patients with focal epilepsy and 15 control subjects...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334640/mirnas-in-synapse-development-and-synaptic-plasticity
#4
REVIEW
Zhonghua Hu, Zheng Li
Synapses are functional units of the nervous system, through which information is transferred between neurons. The development and activity-dependent modification of synapses require temporally and spatially controlled modulation of gene expression. microRNAs (miRNAs) have emerged as essential regulators of gene expression. They are small non-coding RNAs that regulate mRNA stability and translation by interacting with the 3' untranslated region (3' UTR) of mRNAs. miRNAs are located to neuronal processes to regulate protein synthesis locally and their expression is regulated by synaptic activity...
March 20, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28334601/a-tale-of-two-inputs
#5
James Ashley, Vivian Budnik
In this issue of Neuron, Newman et al. (2017) image calcium events at single synapses of unanesthetized Drosophila larvae. Synaptic plasticity and homeostatic regulation of synapses is established to be input specific. Furthermore, plasticity forms involve selective recruitment of previously active or silent synapses.
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334351/effects-of-antenatal-maternal-depressive-symptoms-and-socio-economic-status-on-neonatal-brain-development-are-modulated-by-genetic-risk
#6
Anqi Qiu, Mojun Shen, Claudia Buss, Yap-Seng Chong, Kenneth Kwek, Seang-Mei Saw, Peter D Gluckman, Pathik D Wadhwa, Sonja Entringer, Martin Styner, Neerja Karnani, Christine M Heim, Kieran J O'Donnell, Joanna D Holbrook, Marielle V Fortier, Michael J Meaney
This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume...
March 18, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334325/endocannabinoid-dependent-long-term-potentiation-of-synaptic-transmission-at-rat-barrel-cortex
#7
Laura Eva Maglio, José Antonio Noriega-Prieto, Maria Jesús Maraver, David Fernández de Sevilla
Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition...
March 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334166/grk5-regulates-social-behavior-via-suppression-of-mtorc1-signaling-in-medial-prefrontal-cortex
#8
Bing Niu, Peipei Liu, Minjie Shen, Cao Liu, Li Wang, Feifei Wang, Lan Ma
Impairments in social behaviors are features of a number of psychiatric diseases associated with subtle alterations in the medial prefrontal cortex (mPFC) circuitry. G protein-coupled receptor kinase (GRK) 5 is widely expressing in the cortex, however, its role in regulation of the mPFC activity and the development of social behaviors and psychiatric disorders is unclear. Here, we found that GRK5 dificiency in mice caused social behavior impairments. Further morphological, electrophysiological, and biochemical analyses showed abnormal postsynaptic ultrastructure, impaired excitatory synaptic transmission, the increased association of raptor with mTOR, and overactivated mTORC1-S6K signaling in the mPFC of Grk5-/- mice...
February 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334149/higher-striatal-iron-concentration-is-linked-to-frontostriatal-underactivation-and-poorer-memory-in-normal-aging
#9
Grégoria Kalpouzos, Benjamín Garzón, Rouslan Sitnikov, Carmel Heiland, Alireza Salami, Jonas Persson, Lars Bäckman
In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334142/layer-specific-organization-of-local-excitatory-and-inhibitory-synaptic-connectivity-in-the-rat-presubiculum
#10
Yangfan Peng, Federico J Barreda Tomás, Constantin Klisch, Imre Vida, Jörg R P Geiger
The presubiculum is part of the parahippocampal spatial navigation system and contains head direction and grid cells upstream of the medial entorhinal cortex. This position within the parahippocampal cortex renders the presubiculum uniquely suited for analyzing the circuit requirements underlying the emergence of spatially tuned neuronal activity. To identify the local circuit properties, we analyzed the topology of synaptic connections between pyramidal cells and interneurons in all layers of the presubiculum by testing 4250 potential synaptic connections using multiple whole-cell recordings of up to 8 cells simultaneously...
February 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28333590/mean-first-passage-memory-lifetimes-by-reducing-complex-synapses-to-simple-synapses
#11
Terry Elliott
Memory models that store new memories by forgetting old ones have memory lifetimes that are rather short and grow only logarithmically in the number of synapses. Attempts to overcome these deficits include "complex" models of synaptic plasticity in which synapses possess internal states governing the expression of synaptic plasticity. Integrate-and-express, filter-based models of synaptic plasticity propose that synapses act as low-pass filters, integrating plasticity induction signals before expressing synaptic plasticity...
March 23, 2017: Neural Computation
https://www.readbyqxmd.com/read/28333586/modulation-of-context-dependent-spatiotemporal-patterns-within-packets-of-spiking-activity
#12
Miho Itoh, Timothée Leleu
Recent experiments have shown that stereotypical spatiotemporal patterns occur during brief packets of spiking activity in the cortex, and it has been suggested that top-down inputs can modulate these patterns according to the context. We propose a simple model that may explain important features of these experimental observations and is analytically tractable. The key mechanism underlying this model is that context-dependent top-down inputs can modulate the effective connection strengths between neurons because of short-term synaptic depression...
March 23, 2017: Neural Computation
https://www.readbyqxmd.com/read/28333583/an-approximation-of-the-error-backpropagation-algorithm-in-a-predictive-coding-network-with-local-hebbian-synaptic-plasticity
#13
James C R Whittington, Rafal Bogacz
To efficiently learn from feedback, cortical networks need to update synaptic weights on multiple levels of cortical hierarchy. An effective and well-known algorithm for computing such changes in synaptic weights is the error backpropagation algorithm. However, in this algorithm, the change in synaptic weights is a complex function of weights and activities of neurons not directly connected with the synapse being modified, whereas the changes in biological synapses are determined only by the activity of presynaptic and postsynaptic neurons...
March 23, 2017: Neural Computation
https://www.readbyqxmd.com/read/28332716/mir-124-and-mir-9-mediated-downregulation-of-hdac5-promotes-neurite-development-through-activating-mef2c-gpm6a-pathway
#14
Xi Gu, Congcong Fu, Lifang Lin, Shuhu Liu, Xiaohong Su, Aili Li, Qiaoqi Wu, Chunhong Jia, Peidong Zhang, Lu Chen, Xinhong Zhu, Xuemin Wang
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28332150/dynamic-nature-of-presenilin1-%C3%AE-secretase-implication-for-alzheimer-s-disease-pathogenesis
#15
REVIEW
Katarzyna Marta Zoltowska, Oksana Berezovska
Presenilin 1 (PS1) is a catalytic component of the γ-secretase complex, responsible for the intramembraneous cleavage of more than 90 type I transmembrane proteins, including Alzheimer's disease (AD)-related amyloid precursor protein (APP). The γ-secretase-mediated cleavage of the APP C-terminal membrane stub leads to the production of various amyloid β (Aβ) species. The assembly of Aβ into neurotoxic oligomers, which causes synaptic dysfunction and neurodegeneration, is influenced by the relative ratio of the longer (Aβ42/43) to shorter Aβ (Aβ40) peptides...
March 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28331029/the-sac1-domain-in-synaptojanin-is-required-for%C3%A2-autophagosome-maturation-at-presynaptic%C3%A2-terminals
#16
Roeland Vanhauwaert, Sabine Kuenen, Roy Masius, Adekunle Bademosi, Julia Manetsberger, Nils Schoovaerts, Laura Bounti, Serguei Gontcharenko, Jef Swerts, Sven Vilain, Marina Picillo, Paolo Barone, Shashini T Munshi, Femke Ms de Vrij, Steven A Kushner, Natalia V Gounko, Wim Mandemakers, Vincenzo Bonifati, Frederic A Meunier, Sandra-Fausia Soukup, Patrik Verstreken
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in Synaptojanin(RQ) knock-in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes...
March 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28330777/altered-visual-repetition-suppression-in-fragile-x-syndrome-new-evidence-from-erps-and-oscillatory-activity
#17
Simon Rigoulot, Inga S Knoth, Marc-Philippe Lafontaine, Phetsamone Vannasing, Philippe Major, Sébastien Jacquemont, Jacques L Michaud, Karim Jerbi, Sarah Lippe
Fragile X Syndrome (FXS) is a neurodevelopmental genetic disorder associated with cognitive and behavioural deficits. In particular, neuronal habituation processes have been shown to be altered in FXS patients. Yet, while such deficits have been primarily explored using auditory stimuli, less is known in the visual modality. Here, we investigated the putative alteration of repetition suppression using faces in FXS patients compared to controls that had the same age distribution. Electroencephalographic (EEG) signals were acquired while participants were presented with 18 different faces, each repeated ten times successively...
March 19, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28330719/nicotinamide-mononucleotide-inhibits-jnk-activation-to-reverse-alzheimer-disease
#18
Zhiwen Yao, Wenhao Yang, Zhiqiang Gao, Peng Jia
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice...
March 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28329692/organization-of-functional-long-range-circuits-controlling-the-activity-of-serotonergic-neurons-in-the-dorsal-raphe-nucleus
#19
Li Zhou, Ming-Zhe Liu, Qing Li, Juan Deng, Di Mu, Yan-Gang Sun
Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329674/%C3%AE-arrestin2-couples-metabotropic-glutamate-receptor-5-to-neuronal-protein-synthesis-and-is-a-potential-target-to-treat-fragile-x
#20
Laura J Stoppel, Benjamin D Auerbach, Rebecca K Senter, Anthony R Preza, Robert J Lefkowitz, Mark F Bear
Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu5), yet how mGlu5 couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that β-arrestin2 mediates mGlu5-stimulated protein synthesis in the hippocampus and show that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1(-/y) mouse model of FX...
March 21, 2017: Cell Reports
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