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https://www.readbyqxmd.com/read/28326933/attenuation-of-hyperalgesia-responses-via-the-modulation-of-5-hydroxytryptamine-signalings-in-the-rostral-ventromedial-medulla-and-spinal-cord-in-a-6-hydroxydopamine-induced-rat-model-of-parkinson-s-disease
#1
Chen-Tao Wang, Cheng-Jie Mao, Xiao-Qi Zhang, Cai-Yi Zhang, Dong-Jun Lv, Ya-Ping Yang, Kai-Lin Xia, Jun-Yi Liu, Fen Wang, Li-Fang Hu, Guang-Yin Xu, Chun-Feng Liu
Background Although pain is one of the most distressing non-motor symptoms among patients with Parkinson's disease, the underlying mechanisms of pain in Parkinson's disease remain elusive. The aim of the present study was to investigate the role of serotonin (5-hydroxytryptamine) in the rostral ventromedial medulla (RVM) and spinal cord in pain sensory abnormalities in a 6-hydroxydopamine-treated rat model of Parkinson's disease. Methods The rotarod test was used to evaluate motor function. The radiant heat test and von Frey test were conducted to evaluate thermal and mechanical pain thresholds, respectively...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28324764/enhancing-mitofusin-marf-ameliorates-neuromuscular-dysfunction-in-drosophila-models-of-tdp-43-proteinopathies
#2
Bilal Khalil, Marie-Jeanne Cabirol-Pol, Laetitia Miguel, Alexander J Whitworth, Magalie Lecourtois, Jean-Charles Liévens
Transactive response DNA-binding protein 43 kDa (TDP-43) is considered a major pathological protein in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The precise mechanisms by which TDP-43 dysregulation leads to toxicity in neurons are not fully understood. Using TDP-43-expressing Drosophila, we examined whether mitochondrial dysfunction is a central determinant in TDP-43 pathogenesis. Expression of human wild-type TDP-43 in Drosophila neurons results in abnormally small mitochondria...
February 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28324169/roles-of-centromedian-parafascicular-nuclei-of-thalamus-and-cholinergic-interneurons-in-the-dorsal-striatum-in-associative-learning-of-environmental-events
#3
REVIEW
Ko Yamanaka, Yukiko Hori, Takafumi Minamimoto, Hiroshi Yamada, Naoyuki Matsumoto, Kazuki Enomoto, Toshihiko Aosaki, Ann M Graybiel, Minoru Kimura
The thalamus provides a massive input to the striatum, but despite accumulating evidence, the functions of this system remain unclear. It is known, however, that the centromedian (CM) and parafascicular (Pf) nuclei of the thalamus can strongly influence particular striatal neuron subtypes, notably including the cholinergic interneurons of the striatum (CINs), key regulators of striatal function. Here, we highlight the thalamostriatal system through the CM-Pf to striatal CINs. We consider how, by virtue of the direct synaptic connections of the CM and PF, their neural activity contributes to the activity of CINs and striatal projection neurons (SPNs)...
March 21, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28321933/exploring-the-cause-of-aggregation-and-reduced-zn-binding-affinity-by-g85r-mutation-in-sod1-rendering-amyotrophic-lateral-sclerosis
#4
E Srinivasan, R Rajasekaran
Amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disorder is characterized by the degeneration of upper and lower motor neuron. ALS occurs due to various notably prominent missense mutations, in gene encoding Cu-Zn superoxide dismutase (SOD1) thereby leading to aggregation, dysfunction and reduced Zn binding affinity. In this study, one such mutation, G85R was explored in comparison with wild type SOD1, using discrete molecular dynamics (DMD). Accordingly, the conformational changes were significantly observed in mutant SOD1, through various geometrical parameters, which substantiated the difference in conformational deviation, flexibility and compactness, thus stipulating a root cause for aggregation...
March 21, 2017: Proteins
https://www.readbyqxmd.com/read/28321600/post-6-ohda-lesion-exposure-to-stress-affects-neurotrophic-factor-expression-and-aggravates-motor-impairment
#5
Phumzile Nomfundo Ngema, Musa Vuyisile Mabandla
Chronic exposure to stress amplifies locomotor deficits and exacerbates dopamine neuron loss in an animal model for Parkinson's disease. The release of neurotrophic factors such as glial cell-line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) following neuronal injury attenuates exacerbated degeneration of these neurons. In this study, the neurotoxin 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle of male Sprague Dawley rats. A subset of these rats was subjected to post-lesion restraint stress after which the effect of exposure to stress on locomotor activity (forelimb akinesia test), neurotrophic factor (GDNF and NT-3) and corticosterone concentration was assessed...
March 20, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28320278/cooperative-synthesis-of-dopamine-in-rat-mediobasal-hypothalamus-as-a-compensatory-mechanism-in-hyperprolactinemia
#6
A U Kurina, T S Pronina, L K Dilmukhametova, G V Maleev, M V Ugrumov
Dopamine (DA), synthesized in the mediobasal hypothalamus by dopaminergic neurons containing two enzymes of DA synthesis - tyrosine hydroxylase and decarboxylase of aromatic L-amino acids, or by monoenzymatic non-dopaminergic neurons containing one DA synthesis enzyme in cooperation, is known to have an inhibitory effect on prolactin secretion. Deterioration of this inhibitory control leads to an increase in prolactin concentration in the blood and to the development of hyperprolactinemia syndrome. In a rat model of hyperprolactinemia induced by administration of a neurotoxin causing degeneration of dopaminergic and noradrenergic neurons, the level of DA first decreases, leading to an increase in prolactin level (decompensation stage), while later both levels are restored to normal (compensation stage)...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28315278/peeking-into-sigma-1-receptor-functions-through-the-retina
#7
Timur A Mavlyutov, Lian-Wang Guo
This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315275/sigma-1-receptor-in-motoneuron-disease
#8
Renzo Mancuso, Xavier Navarro
Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315260/introduction-to-sigma-receptors-their-role-in-disease-and-as-therapeutic-targets
#9
Sylvia B Smith
This book highlights contributions from leaders in the field of sigma receptor research. Sigma receptors represent a promising, novel target for the treatment of neurodegenerative diseases, retinal degenerations, pain and substance abuse. Information is presented about tracers for molecular imaging these receptors, the newly determined crystal structure of human sigma 1 receptor and information about sigma 2 receptor. New discoveries about the role of sigma 1 receptors in cancer, pain, neuropsychiatric disorders, learning and memory, neuronal networks and depression are described...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28306638/the-proinflammatory-cytokines-il-1%C3%A3-and-tnf-%C3%AE-influence-human-annulus-cell-signaling-cues-for-neurite-growth-in-vitro-co-culture-studies
#10
Helen E Gruber, Brittany Jones, Emilio Marrero, Edward N Hanley
STUDY DESIGN: IRB-approved research using human annulus cells co-cultured with F11 nerve cells. OBJECTIVE: To perform functional, kinetic assays of neurite dynamics and media neurotrophin measurement to test whether proinflammatory cytokines influence annulus cells' signaling cues for neurite growth/repulsion. SUMMARY OF BACKGROUND DATA: Nerves grow in response to signaling molecules called neurotrophins which disc cells produce (e.g. brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF) and neurotrophin 3 (NT3)) and which influence neuron survival, differentiation and migration...
March 16, 2017: Spine
https://www.readbyqxmd.com/read/28304238/remote-motor-system-metabolic-profile-and-surgery-outcome-in-cervical-spondylotic-myelopathy
#11
Sorin C Craciunas, Mircea R Gorgan, Bogdan Ianosi, Phil Lee, Joseph Burris, Carmen M Cirstea
OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities...
March 17, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#12
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28302159/a-data-driven-approach-links-microglia-to-pathology-and-prognosis-in-amyotrophic-lateral-sclerosis
#13
Johnathan Cooper-Knock, Claire Green, Gabriel Altschuler, Wenbin Wei, Joanna J Bury, Paul R Heath, Matthew Wyles, Catherine Gelsthorpe, J Robin Highley, Alejandro Lorente-Pons, Tim Beck, Kathryn Doyle, Karel Otero, Bryan Traynor, Janine Kirby, Pamela J Shaw, Winston Hide
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that lacks a predictive and broadly applicable biomarker. Continued focus on mutation-specific upstream mechanisms has yet to predict disease progression in the clinic. Utilising cellular pathology common to the majority of ALS patients, we implemented an objective transcriptome-driven approach to develop noninvasive prognostic biomarkers for disease progression. Genes expressed in laser captured motor neurons in direct correlation (Spearman rank correlation, p < 0...
March 16, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28301478/retrotransposon-activation-contributes-to-neurodegeneration-in-a-drosophila-tdp-43-model-of-als
#14
Lisa Krug, Nabanita Chatterjee, Rebeca Borges-Monroy, Stephen Hearn, Wen-Wei Liao, Kathleen Morrill, Lisa Prazak, Nikolay Rozhkov, Delphine Theodorou, Molly Hammell, Josh Dubnau
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28301218/retinal-pathology-is-associated-with-increased-blood-retina-barrier-permeability-in-a-diabetic-and-hypercholesterolaemic-pig-model-beneficial-effects-of-the-lppla2-inhibitor-darapladib
#15
Nimish K Acharya, Xin Qi, Eric L Goldwaser, George A Godsey, Hao Wu, Mary C Kosciuk, Theresa A Freeman, Colin H Macphee, Robert L Wilensky, Venkat Venkataraman, Robert G Nagele
Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28300211/als-along-the-axons-expression-of-coding-and-noncoding-rna-differs-in-axons-of-als-models
#16
Nimrod Rotem, Iddo Magen, Ariel Ionescu, Noga Gershoni-Emek, Topaz Altman, Christopher J Costa, Tal Gradus, Metsada Pasmanik-Chor, Dianna E Willis, Iddo Z Ben-Dov, Eran Hornstein, Eran Perlson
Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA)...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299521/dynamic-of-contribution-of-ubpy-sorted-cargo-to-acrosome-biogenesis-effects-of-its-derailment-in-a-mouse-model-of-globozoospermia-the-infertile-vps54-l967q-mutant
#17
Mariarosa Gioria, Maria Enrica Pasini, Giovanna Berruti
The sperm acrosome is a specialized vacuole, a member of the family of cell-specific lysosome-related organelles. Its exocytosis, the acrosome reaction, is a crucial event during fertilization. The released acrosomal contents promote sperm penetration through the investments of the oocyte, whereas the membranous components of the acrosome are involved in sperm-oocyte interaction/fusion and oocyte activation. The way that these functionally distinct acrosomal costituents reach the vacuole during its biogenesis remains poorly understood...
March 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28298170/concussion-induces-hippocampal-circuitry-disruption-in-swine
#18
John A Wolf, Brian N Johnson, Victoria E Johnson, Mary E Putt, Kevin D Browne, Constance J Mietus, Daniel P Brown, Kathryn L Wofford, Douglas H Smith, M Sean Grady, Akiva S Cohen, D Kacy Cullen
Hippocampal-dependent deficits in learning and memory formation are a prominent feature of traumatic brain injury (TBI), however the role of the hippocampus in cognitive dysfunction after concussion (mild TBI) is unknown. We therefore investigated functional and structural changes in the swine hippocampus following TBI using a model of head rotational acceleration that closely replicates the biomechanics and neuropathology of closed-head TBI in humans. We examined neurophysiological changes using a novel ex vivo hippocampal slice paradigm with extracellular stimulation and recording in the dentate gyrus and CA1 occurring at 7 days following non-impact inertial TBI in swine...
March 16, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28296388/degradable-semiconducting-oligomer-amphiphile-for-ratiometric-photoacoustic-imaging-of-hypochlorite
#19
Chao Yin, Xu Zhen, Quli Fan, Wei Huang, Kanyi Pu
Upregulation of highly reactive oxygen species (ROS) such as hypochlorite (ClO-) is associated with many pathological conditions including cardiovascular diseases, neuron degeneration, lung injury and cancer. However, real-time imaging of ClO- is limited to the probes generally relying on fluorescence with shallow tissue-penetration depth. We here propose a self-assembly approach to develop activatable and degradable photoacoustic (PA) nanoprobes for in vivo imaging of ClO-. A near-infrared (NIR) absorbing amphiphilic oligomer was synthesized to undergo degradation in the presence of a specific ROS (ClO-), which integrates a π-conjugated but ClO- oxidizable backbone with hydrophilic PEG side chains...
March 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/28294337/copper-increases-the-ability-of-6-hydroxydopamine-to-generate-oxidative-stress-and-the-ability-of-ascorbate-and-glutathione-to-potentiate-this-effect-potential-implications-in-parkinson-s-disease
#20
Antón Cruces-Sande, Estefanía Méndez-Álvarez, Ramón Soto-Otero
Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals...
March 14, 2017: Journal of Neurochemistry
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