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https://www.readbyqxmd.com/read/28439226/the-phosphodiesterase-10a-inhibitor-pf-2545920-enhances-hippocampal-excitability-and-seizure-activity-involving-the-upregulation-of-glua1-and-nr2a-in-post-synaptic-densities
#1
Yanke Zhang, Baobing Gao, Fangshuo Zheng, Shanshan Lu, Yun Li, Yan Xiong, Qin Yang, Yong Yang, Pengfei Fu, Fei Xiao, Xuefeng Wang
Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted attention as a potential therapy for neurological and psychiatric disorders. We hypothesized that PF-2545920 plays an important role in status epilepticus (SE) and investigated the underlying mechanisms...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28437460/an-aggregation-removal-model-for-the-formation-and-size-determination-of-post-synaptic-scaffold-domains
#2
Jonas Ranft, Leandro G Almeida, Pamela C Rodriguez, Antoine Triller, Vincent Hakim
The formation and stability of synapses are key questions in neuroscience. Post-synaptic domains have been classically conceived as resulting from local insertion and turnover of proteins at the synapse. However, insertion is likely to occur outside the post-synaptic domains and advances in single-molecule imaging have shown that proteins diffuse in the plane of the membrane prior to their accumulation at synapses. We quantitatively investigated this scenario using computer simulations and mathematical analysis, taking for definiteness the specific case of inhibitory synapse components, i...
April 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28437436/intrinsically-generated-fluctuating-activity-in-excitatory-inhibitory-networks
#3
Francesca Mastrogiuseppe, Srdjan Ostojic
Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive...
April 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28436658/chemical-composition-and-acetylcholinesterase-inhibitory-activity-of-essential-oils-from-piper-species
#4
Cai-Peng Xiang, Jia-Xin Han, Xing-Cong Li, Yun-Hui Li, Yi Zhang, Lin Chen, Yan Qu, Chao-Yun Hao, Hai-Zhou Li, Chong-Ren Yang, San-Jun Zhao, Min Xu
The essential oils (EOs) derived from aromatic plants such as Piper species are considered to play a role in alleviating neuronal ailments that are associated with inhibition of acetylcholinesterase (AChE). The chemical compositions of 23 EOs prepared from 16 Piper spp. were analyzed by both gas chromatography with aflame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). A total of 76 compounds were identified in the EOs from the leaves and stems of 19 samples, while 30 compounds were detected in the EOs from the fruits of four samples...
April 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28436626/-the-role-of-central-cholinergic-system-in-epilepsy
#5
Ying Wang, Yi Wang, Zhong Chen
Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28436443/curcumol-allosterically-modulates-gaba-a-receptors-in-a-manner-distinct-from-benzodiazepines
#6
Yan-Mei Liu, Hui-Ran Fan, Jing Ding, Chen Huang, Shining Deng, Tailin Zhu, Tian-Le Xu, Wei-Hong Ge, Wei-Guang Li, Fei Li
Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#7
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28434283/considering-tapentadol-as-a-first-line-analgesic-14-questions
#8
Joseph V Pergolizzi, Frank Breve, Robert Taylor, Robert B Raffa, Stephani E Strasburger, Jo Ann LeQuang
Tapentadol is the newest centrally acting analgesic to be approved by the US FDA and regulatory bodies in other countries. It has been called the first-in-class of a novel-acting analgesic mechanism of action that combines µ-opioid receptor agonist activity with neuronal norepinephrine-reuptake inhibition in a single molecule. This duality of action should combine inhibition of ascending (afferent) pain-transmitting signals with activation of descending (efferent) pain-attenuating systems (e.g., diffuse noxious inhibitory controls)...
April 24, 2017: Pain Management
https://www.readbyqxmd.com/read/28434161/can-valproic-acid-regulate-neurogenesis-from-nestin-cells-in-the-adult-midbrain
#9
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) causes the motor symptoms (e.g. tremor, muscle rigidity, bradykinesia, postural instability) of Parkinson's disease (PD). It is generally agreed that replacing these neurons will provide better motor symptom relief and fewer side effects than current pharmacotherapies. One potential approach to this is up-regulating endogenous DA neurogenesis in SNc. In the present study, we conducted bioinformatics analyses to identify signalling pathways that control expression of Pax6 and Msx1 genes, which have been identified as potentially important neurogenic regulators in the adult midbrain...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28432980/discovery-of-potential-inhibitor-against-human-acetylcholinesterase-a-molecular-docking-and-molecular-dynamics-investigation
#10
Surya Pratap Singh, Dwijendra Gupta
Alzheimer's disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE...
April 12, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28432786/the-comprehensive-connectome-of-a-neural-substrate-for-on-motion-detection-in-drosophila
#11
Shin-Ya Takemura, Aljoscha Nern, Dmitri B Chklovskii, Louis K Scheffer, Gerald M Rubin, Ian A Meinertzhagen
Analysing computations in neural circuits often uses simplified models because the actual neuronal implementation is not known. For example, a problem in vision, how the eye detects image motion, has long been analysed using Hassenstein-Reichardt (HR) detector or Barlow-Levick (BL) models. These both simulate motion detection well, but the exact neuronal circuits undertaking these tasks remain elusive. We reconstructed a comprehensive connectome of the circuits of Drosophila's motion-sensing T4 cells using a novel EM technique...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432601/neuropathic-pain-central-vs-peripheral-mechanisms
#12
REVIEW
Kathleen Meacham, Andrew Shepherd, Durga P Mohapatra, Simon Haroutounian
PURPOSE OF REVIEW: Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial...
June 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28432332/involvement-of-gonadotropin-inhibitory-hormone-in-pubertal-disorders-induced-by-thyroid-status
#13
Mika Kiyohara, You Lee Son, Kazuyoshi Tsutsui
Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#14
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432141/the-spacing-effect-for-structural-synaptic-plasticity-provides-specificity-and-precision-in-plastic-changes
#15
Martin A San, L Rela, B D Gelb, M R Pagani
In contrast to trials of training without intervals (massed training), training trials spaced over time (spaced training) induce a more persistent memory identified as long-term memory (LTM). This phenomenon known as "the spacing effect for memory" is poorly understood. LTM is supported by structural synaptic plasticity; however, how synapses integrate spaced stimuli remains elusive. Here, we analyzed events of structural synaptic plasticity at the single synapse level after distinct patterns of stimulation in motoneurons of Drosophila We found that the spacing effect is a phenomenon detected at synaptic level, which determine the specificity and the precision in structural synaptic plasticity...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432140/visually-evoked-3-5-hz-membrane-potential-oscillations-reduce-the-responsiveness-of-visual-cortex-neurons-in-awake-behaving-mice
#16
Michael C Einstein, Pierre-Olivier Polack, Duy T Tran, Peyman Golshani
Low frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low frequency Vm oscillations have been described in inactive awake animals, but it is unclear if they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28431434/bright-light-suppresses-form-deprivation-myopia-development-with-activation-of-dopamine-d1-receptor-signaling-in-the-on-pathway-in-retina
#17
Si Chen, Zhina Zhi, Qingqing Ruan, Qingxia Liu, Fen Li, Fen Wan, Peter S Reinach, Jiangfan Chen, Jia Qu, Xiangtian Zhou
Purpose: To determine whether dopamine receptor D1 (D1R) signaling pathway activation by bright light (BL) in specific retinal neuronal cell types contributes to inhibiting form-deprivation myopia (FDM) in mice. Methods: Mice (3-weeks old) were raised under either normal light (NL: 100-200 lux) or BL (2500-5000 lux) conditions with or without form deprivation. Refraction changes were evaluated with an eccentric infrared photorefractor, and ocular axial components with optical coherence tomography...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28430864/the-gnih-lpxrfa-system-s-regulation-of-reproduction-in-the-brain-pituitary-axis-of-the-zebrafish-danio-rerio
#18
Olivia Smith Spicer, Nilli Zmora, Ten-Tsao Wong, Matan Golan, Berta Levavi-Sivan, Yoav Gothilf, Yonathan Zohar
Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (Lpxrfa peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28429571/melatonin-antagonizes-interleukin-18-mediated-inhibition-on-neural-stem-cell-proliferation-and-differentiation
#19
Zheng Li, Xingye Li, Matthew T V Chan, William Ka Kei Wu, DunXian Tan, Jianxiong Shen
Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18)...
April 21, 2017: Journal of Cellular and Molecular Medicine
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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