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Experimental Neurology

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https://www.readbyqxmd.com/read/28342750/mutation-of-the-caspase-3-cleavage-site-in-the-astroglial-glutamate-transporter-eaat2-delays-disease-progression-and-extends-lifespan-in-the-sod1-g93a-mouse-model-of-als
#1
Lauren Taylor Rosenblum, Shashirekha Shamamandri-Markandaiah, Biswarup Ghosh, Emily Foran, Angelo C Lepore, Piera Pasinelli, Davide Trotti
Downregulation in the astroglial glutamate transporter EAAT2 in amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 mouse models of ALS is believed to contribute to the death of motor neurons by excitotoxicity. We previously reported that caspase-3 cleaves EAAT2 at a unique cleavage consensus site located in its c-terminus domain, a proteolytic cleavage that also occurs in vivo in the mutant SOD1 mouse model of ALS and leads to accumulation of a sumoylated EAAT2 C-Terminus fragment (CTE-SUMO1) beginning around onset of disease...
March 22, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28342749/characterizing-the-differential-roles-of-striatal-5-ht1a-auto-and-hetero-receptors-in-the-reduction-of-l-dopa-induced-dyskinesia
#2
Samantha M Meadows, Nicole Chambers, Melissa M Conti, Sharon C Bossert, Crystal Tasber, Eitan Sheena, Mark Varney, Adrian Newman-Tancredi, Christopher Bishop
l-DOPA remains the benchmark treatment for Parkinson's disease (PD) motor symptoms, but chronic use leads to l-DOPA-induced dyskinesia (LID). The serotonin (5-HT) system has been established as a key modulator of LID and 5-HT1A receptors (5-HT1AR) stimulation has been shown to convey anti-dyskinetic effects. However, 5-HT1AR agonists often compromise clinical efficacy or display intrinsic side effects and their site(s) of actions remain debatable. Recently, highly selective G-protein biased 5-HT1AR agonists, F13714 and F15599, were shown to potently target 5-HT1A auto- or hetero-receptors, respectively...
March 22, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28342748/rnai-of-arcrna-hsr%C3%AF-affects-sub-cellular-localization-of-drosophila-fus-to-drive-neurodiseases
#3
Luca Lo Piccolo, Masamitsu Yamaguchi
Defective RNA metabolism is common pathogenic mechanisms involved in neurological disorders. Indeed, a conspicuous feature of some neurodegenerative diseases is the loss of nuclear activities of RNA-binding proteins (RBPs) like Fused in sarcoma (FUS) and eventually, their accumulation in cytoplasmic proteinaceous inclusions. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes, including neurological disorders. A subset of these lncRNAs is the core of nuclear bodies (NBs), which are the sites of RNA processing and sequestration of specific ribonucleoproteins (RNPs) complexes...
March 22, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28342747/subthalamic-nucleus-beta-and-gamma-activity-is-modulated-depending-on-the-level-of-imagined-grip-force
#4
Petra Fischer, Alek Pogosyan, Binith Cheeran, Alexander L Green, Tipu Z Aziz, Jonathan Hyam, Simon Little, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Marwan Hariz, Michael Samuel, Keyoumars Ashkan, Peter Brown, Huiling Tan
Motor imagery involves cortical networks similar to those activated by real movements, but the extent to which the basal ganglia are recruited is not yet clear. Gamma and beta oscillations in the subthalamic nucleus (STN) vary with the effort of sustained muscle activity. We recorded local field potentials in Parkinson's disease patients and investigated if similar changes can be observed during imagined gripping at three different 'forces'. We found that beta activity decreased significantly only for imagined grips at the two stronger force levels...
March 22, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28341461/sequential-therapy-of-anti-nogo-a-antibody-treatment-and-treadmill-training-leads-to-cumulative-improvements-after-spinal-cord-injury-in-rats
#5
Kinon Chen, Barnaby C Marsh, Matthew Cowan, Yazi D Al'Joboori, Sylvain Gigout, Calvin C Smith, Neil Messenger, Nikita Gamper, Martin E Schwab, Ronaldo M Ichiyama
Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2weeks) and then either left untrained or step-trained starting 3weeks after injury for 8weeks...
March 21, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28341460/cortical-adrenoceptor-expression-function-and-adaptation-under-conditions-of-cannabinoid-receptor-deletion
#6
B A S Reyes, A F Carvalho, P Szot, D J Kalamarides, Q Wang, L G Kirby, E J Van Bockstaele
A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid-induced 1) increases in norepinephrine (NE) release in the medial prefrontal cortex (mPFC); 2) desensitization of cortical α2-adrenoceptor-mediated effects; 3) activation of c-Fos in brainstem locus coeruleus (LC) noradrenergic neurons; and 4) increases in anxiety-like behaviors...
March 21, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28336394/ts1cje-down-syndrome-model-mice-exhibit-environmental-stimuli-triggered-locomotor-hyperactivity-and-sociability-concurrent-with-increased-flux-through-central-dopamine-and-serotonin-metabolism
#7
Atsushi Shimohata, Keiichi Ishihara, Satoko Hattori, Hiroyuki Miyamoto, Hiromasa Morishita, Guy Ornthanalai, Matthieu Raveau, Abdul Shukkur Ebrahim, Kenji Amano, Kazuyuki Yamada, Haruhiko Sago, Satoshi Akiba, Nobuko Mataga, Niall P Murphy, Tsuyoshi Miyakawa, Kazuhiro Yamakawa
Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice...
March 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28322742/potassium-channel-abnormalities-are-consistent-with-early-axon-degeneration-of-motor-axons-in-the-g127x-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#8
Rikke Maglemose, Anne Hedegaard, Janna Lehnhoff, Kristina Petrova Dimintiyanova, Mihai Moldovan, Lillian Grøndahl, Claire Francesca Meehan
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects upper and lower motoneurones. The underlying pathophysiology of the disease is complex but electrophysiological studies of peripheral nerves in ALS patients as well as human autopsy studies indicate that a potassium channel dysfunction/loss is present early in the symptomatic phase. It remains unclear to what extent potassium channel abnormalities reflect a specific pathogenic mechanism in ALS. The aim of this study was therefore to investigate the temporal changes in the expression and/or function of potassium channels in motoneurones in the adult G127X SOD1 mouse model of ALS, a model which has a very long presymptomatic phase...
March 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28315308/target-specific-alterations-in-the-vip-inhibitory-drive-to-hippocampal-gabaergic-cells-after-status-epilepticus
#9
Linda Suzanne David, Lisa Topolnik
Status epilepticus (SE) is associated with complex reorganization of hippocampal circuits involving a significant loss of specific subtypes of GABAergic interneurons. While adaptive circuit plasticity may increase the chances for recruitment of surviving interneurons, the underlying mechanisms remain largely unknown. We studied the alterations in the inhibitory tone received by the hippocampal CA1 oriens/alveus (O/A) interneurons from the vasoactive intestinal peptide (VIP)- and calretinin (CR)-expressing interneurons using the pilocarpine-induced status epilepticus (SE) model of epilepsy...
March 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28292530/corrigendum-to-reggie-1-and-reggie-2-flotillins-participate-in-rab11a-dependent-cargo-trafficking-spine-synapse-formation-and-ltp-related-ampa-receptor-glua1-surface-exposure-in-mouse-hippocampal-neurons-exp-neurol-289-pages-31-45
#10
Vsevolod Bodrikov, Aline Pauschert, Gaga Kochlamazashvili, Claudia A O Stuermer
No abstract text is available yet for this article.
March 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28291520/corrigendum-to-entorhinal-cortex-lesions-result-in-adenosine-sensitive-high-frequency-oscillations-in-the-hippocampus-exp-neurol-271-2015-319-328
#11
Franco Ortiz, Rafael Gutiérrez
No abstract text is available yet for this article.
March 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28284817/differential-effects-of-gaseous-versus-injectable-anesthetics-on-changes-in-regional-cerebral-blood-flow-and-metabolism-induced-by-l-dopa-in-a-rat-model-of-parkinson-s-disease
#12
Zisis Bimpisidis, Carl M Öberg, Natallia Maslava, M Angela Cenci, Cornelia Lundblad
Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-2-deoxyglucose) with a highly sensitive autoradiographic method...
March 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28283336/tissue-engineering-with-peripheral-blood-derived-mesenchymal-stem-cells-promotes-the-regeneration-of-injured-peripheral-nerves
#13
Mengjie Pan, Xianghai Wang, Yijing Chen, Shangtao Cao, Jinkun Wen, Guofeng Wu, Yuanyuan Li, Lixia Li, Changhui Qian, Zhenqi Qin, Zhenlin Li, Dandan Tan, Zhihao Fan, Wutian Wu, Jiasong Guo
Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP...
March 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28274862/diabetic-aggravation-of-stroke-and-animal-models
#14
REVIEW
Ashish K Rehni, Allen Liu, Miguel A Perez-Pinzon, Kunjan R Dave
Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia currently being employed to study diabetes-related ischemic brain damage...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28274861/defining-the-biomechanical-and-biological-threshold-of-murine-mild-traumatic-brain-injury-using-chimera-closed-head-impact-model-of-engineered-rotational-acceleration
#15
Dhananjay R Namjoshi, Wai Hang Cheng, Asma Bashir, Anna Wilkinson, Sophie Stukas, Kris M Martens, Tom Whyte, Zelalem A Abebe, Kurt A McInnes, Peter A Cripton, Cheryl L Wellington
CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28274860/purinergic-2x7-receptor-nlrp3-pathway-triggers-neuronal-apoptosis-after-ischemic-stroke-in-the-mouse
#16
Xinchun Ye, Tong Shen, Jinxia Hu, Liang Zhang, Yunshan Zhang, Lei Bao, Chengcheng Cui, Guoliang Jin, Kun Zan, Zuohui Zhang, Xinxin Yang, Hongjuan Shi, Jie Zu, Ming Yu, Chengjie Song, Yulan Wang, Suhua Qi, Guiyun Cui
Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950)...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#17
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28223038/nanoconjugate-bound-adenosine-a1-receptor-antagonist-enhances-recovery-of-breathing-following-acute-cervical-spinal-cord-injury
#18
Zeljka Minic, Sharowyn Wilson, Fangchao Liu, Abdulghani Sankari, Guangzhao Mao, Harry Goshgarian
Respiratory complications in patients with spinal cord injury (SCI) are common and can have a negative impact on the quality of patients' lives. Previously, we found that intradiaphragmatic administration of the nanoconjugate-bound A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) induced recovery of diaphragm function following SCI in rats. When administered immediately following the injury, recovery was observed as early as 3days following SCI and it persisted until the end of the study, 28days after the drug delivery...
February 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28223037/asymmetric-dopaminergic-degeneration-and-levodopa-alter-functional-corticostriatal-connectivity-bilaterally-in-experimental-parkinsonism
#19
Cyril Monnot, Xiaoqun Zhang, Sahar Nikkhou-Aski, Peter Damberg, Per Svenningsson
Asymmetric dopamine loss is commonly found in early Parkinson's disease (PD), but its effects on functional networks have been difficult to delineate in PD patients because of variations in age, disease duration and therapy. Here we used unilateral 6-hydroxydopamine-lesioned (6-OHDA) rats and controls and treated them with a single intraperitoneal injection of levodopa (L-DOPA) before performing diffusion weighted MRI and resting state functional MRI (rs-fMRI). In accordance with a neurodegeneration of the nigrostriatal dopaminergic pathway, diffusion tensor imaging showed increased radial diffusivity and decreased fractional anisotropy in the lesioned substantia nigra...
February 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28215575/fibronectin-connecting-segment-1-peptide-inhibits-pathogenic-leukocyte-trafficking-and-inflammatory-demyelination-in-experimental-models-of-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#20
Chaoling Dong, Kelsey M Greathouse, Rebecca L Beacham, Steven P Palladino, E Scott Helton, Eroboghene E Ubogu
The molecular determinants of pathogenic leukocyte migration across the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are unknown. Specific disease modifying therapies for CIDP are also lacking. Fibronectin connecting segment-1 (FNCS1), an alternatively spliced fibronectin variant expressed by microvascular endothelial cells at sites of inflammation in vitro and in situ, is a counterligand for leukocyte α4 integrin (also known as CD49d) implicated in pathogenic leukocyte trafficking in multiple sclerosis and inflammatory bowel disease...
February 16, 2017: Experimental Neurology
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