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https://www.readbyqxmd.com/read/28705167/inhibition-of-parkinsonian-tremor-with-cutaneous-afferent-evoked-by-transcutaneous-electrical-nerve-stimulation
#1
Man-Zhao Hao, Shao-Qin Xu, Zi-Xiang Hu, Fu-Liang Xu, Chuan-Xin M Niu, Qin Xiao, Ning Lan
BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS)...
July 14, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28701928/the-hyperpolarization-activated-current-determines-synaptic-excitability-calcium-activity-and-specific-viability-of-substantia-nigra-dopaminergic-neurons
#2
Carmen Carbone, Alessia Costa, Gustavo Provensi, Guido Mannaioni, Alessio Masi
Differential vulnerability between Substantia Nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of Parkinson's disease (PD). Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28697947/synaptic-distribution-and-plasticity-in-primary-auditory-cortex-a1-exhibits-laminar-and-cell-specific-changes-in-the-deaf
#3
H Ruth Clemo, Stephen G Lomber, M Alex Meredith
The processing sequence through primary auditory cortex (A1) is impaired by deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted deaf cats. Such a loss of neuronal excitation should be manifest as changes in excitatory synaptic number and/or size, for which the post-synaptic correlate is the dendritic spine. Therefore, the present study sought evidence for this functional disruption using Golgi-Cox/light microscopic techniques that examined spine-bearing neurons and their dendritic spine features across all laminae in A1 of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and hearing cats...
July 1, 2017: Hearing Research
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#4
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28660571/isolation-of-neuronal-synaptic-membranes-by-sucrose-gradient-centrifugation
#5
Blake R Hopiavuori, Dustin R Masser, Joseph L Wilkerson, Richard S Brush, Nawajes A Mandal, Robert E Anderson, Willard M Freeman
Sucrose gradient centrifugation is a very useful technique for isolating specific membrane types based on their size and density. This is especially useful for detecting fatty acids and lipid molecules that are targeted to specialized membranes. Without fractionation, these types of molecules could be below the levels of detection after being diluted out by the more abundant lipid molecules with a more ubiquitous distribution throughout the various cell membranes. Isolation of specific membrane types where these lipids are concentrated allows for their detection and analysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#6
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28599322/monoamine-oxidase-a-upregulated-by-chronic-intermittent-hypoxia-activates-indoleamine-2-3-dioxygenase-and-neurodegeneration
#7
Chun-Sing Lam, Jing-Jie Li, George Lim Tipoe, Moussa B H Youdim, Man-Lung Fung
Co-morbid depression is prevalent in patients with obstructive sleep apnea. Here we report that monoamine oxidase A (MAO-A) plays pathogenic roles in the comorbidity. We found that chronic intermittent hypoxia significantly increased the MAO-A expression in the rat hippocampus and markedly decreased the dendritic length and spine density in the pyramidal neurons with less pre- and post-synaptic proteins. The MAO-A upregulation resulted in increased 5-hydroxyindoleacetic acid/serotonin ratio, oxidative stress, leading to NF-κB activation, inflammation and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28553222/dynamic-arc-sumoylation-and-selective-interaction-with-f-actin-binding-protein-drebrin-a-in-ltp-consolidation-in-vivo
#8
Rajeevkumar R Nair, Sudarshan Patil, Adrian Tiron, Tambudzai Kanhema, Debabrata Panja, Lars Schiro, Kamil Parobczak, Grzegorz Wilczynski, Clive R Bramham
Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. Post-translation modification by small ubiquitin-like modifier (SUMO) proteins has emerged as a major mechanism for regulating protein-protein interactions and function. We first show in cell lines that ectopically expressed Arc undergoes mono-SUMOylation. The covalent addition of a single SUMO1 protein was confirmed by in vitro SUMOylation of immunoprecipitated Arc...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28545543/inhibition-of-colony-stimulating-factor-1-receptor-early-in-disease-ameliorates-motor-deficits-in-sca1-mice
#9
Wenhui Qu, Andrea Johnson, Joo Hyun Kim, Abigail Lukowicz, Daniel Svedberg, Marija Cvetanovic
BACKGROUND: Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1...
May 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28539417/exposure-to-stressors-facilitates-long-term-synaptic-potentiation-in-the-lateral-habenula
#10
Hoyong Park, Jeehae Rhee, Kwanghoon Park, Jung-Soo Han, Roberto Malinow, ChiHye Chung
The lateral habenula (LHb) is a small part of the epithalamus that projects to monoamine centers in the brain. Previously, neurotransmission onto the LHb was shown to be abnormally potentiated in animal models of depression. However, synaptic plasticity in this brain area and the effect of stressor exposure on synaptic plasticity of the LHb have not been investigated. Thus, we explored whether the LHb undergoes dynamic changes in synaptic efficacy or not. First, we observed that a moderate long-term potentiation (LTP) occurs in a fraction of LHb neurons obtained from naïve Sprague Dawley rats...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#11
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28512860/intrinsic-cellular-and-molecular-properties-of-in-vivo-hippocampal-synaptic-plasticity-are-altered-in-the-absence-of-key-synaptic-matrix-molecules
#12
Stephan Jansen, Christine Gottschling, Andreas Faissner, Denise Manahan-Vaughan
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca(2+) -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO)...
August 2017: Hippocampus
https://www.readbyqxmd.com/read/28473257/stress-and-corticosterone-alter-synaptic-plasticity-in-a-rat-model-of-parkinson-s-disease
#13
YongXin Hao, Aref Shabanpoor, Gerlinde A Metz
As a major influence on neuronal function and plasticity, chronic stress can affect the progression and symptoms of neurodegenerative conditions, such as Parkinson's disease (PD). Here we investigated the influence of unilateral dopamine depletion and stress on dopamine-related hallmarks of stress response and neuronal plasticity in a rat model of PD. Animals received either restraint stress or a combination of adrenalectomy and corticosterone (CORT) supplementation to clamp circulating glucocorticoid levels for three weeks prior to unilateral nigrostriatal dopamine depletion...
June 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28472657/structural-bases-of-desensitization-in-ampa-receptor-auxiliary-subunit-complexes
#14
Edward C Twomey, Maria V Yelshanskaya, Robert A Grassucci, Joachim Frank, Alexander I Sobolevsky
Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28469556/integrative-analysis-of-brain-region-specific-shank3-interactomes-for-understanding-the-heterogeneity-of-neuronal-pathophysiology-related-to-shank3-mutations
#15
Yeunkum Lee, Hyojin Kang, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Won-Ki Kim, Kihoon Han
Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28463587/mild-traumatic-brain-injury-leads-to-decreased-inhibition-and-a-differential-response-of-calretinin-positive-interneurons-in-the-injured-cortex
#16
Mariana Brizuela, Catherine A Blizzard, Jyoti A Chuckowree, Kimberley A Pitman, Kaylene M Young, Tracey Dickson
It is clear that even mild forms of traumatic brain injury (TBI) can have lasting cognitive effects; however, the specific cellular changes responsible for the functional deficits remain poorly understood. Previous studies suggest that not all neurons respond in the same way and that changes to neuronal architecture may be subtype specific. The current study aimed to characterize the response of interneurons to TBI. To model TBI in vitro, the neurites of primary cortical neurons were transected at 15 days in vitro...
June 28, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28442991/a-novel-long-non-coding-rna-durga-modulates-dendrite-density-and-expression-of-kalirin-in-zebrafish
#17
Mayuresh A Sarangdhar, Divya Chaubey, Abhishek Bhatt, Monisha Km, Manish Kumar, Shashi Ranjan, Beena Pillai
Kalirin, a key player in axonal development, nerve growth and synaptic re-modeling, is implicated in many pathological conditions like schizophrenia and autism-spectrum disorders. Alternative promoters and splicing lead to functionally distinct isoforms, but the post-transcriptional regulation of Kalirin has not been studied. Here, we report a novel non-coding RNA, which we name durga, arising from the first exon of kalirin a (kalrna) in the antisense orientation in zebrafish. The kalrna and durga transcripts are barely detectable during early development, but steadily increase by 24 hours post-fertilization (hpf) as the brain develops...
2017: Frontiers in Molecular Neuroscience
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
#18
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/28411102/zl006-protects-spinal-cord-neurons-against-ischemia-induced-oxidative-stress-through-ampk-pgc-1%C3%AE-sirt3-pathway
#19
Shu-Guang Liu, Yun-Mei Wang, Yan-Jun Zhang, Xi-Jing He, Tao Ma, Wei Song, Yu-Min Zhang
Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28397041/effects-of-nourishing-liver-and-kidney-acupuncture-therapy-on-expression-of-brain-derived-neurotrophic-factor-and-synaptophysin-after-cerebral-ischemia-reperfusion-in-rats
#20
Wen-Guang Xia, Chan-Juan Zheng, Xuan Zhang, Juan Wang
The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
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