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Experimental Neurology

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https://www.readbyqxmd.com/read/28928022/the-role-of-jab1-a-putative-downstream-effector-of-the-neurotrophic-cytokine-macrophage-migration-inhibitory-factor-mif-in-zebrafish-inner-ear-hair-cell-development
#1
REVIEW
Loren J Weber, Hannah K Marcy, Yu-Chi Shen, Sarah E Tomkovich, Kristina M Brooks, Kelly E Hilk, Kate F Barald
Macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for inner ear hair cell (HC) development and statoacoustic ganglion (SAG) neurite outgrowth, and SAG survival in mouse, chick and zebrafish. Another neurotrophic cytokine, Monocyte chemoattractant protein 1 (MCP1) is known to synergize with MIF; but MCP1 alone is insufficient to support mouse/chick SAG neurite outgrowth or neuronal survival. Because of the relatively short time over which the zebrafish inner ear develops (~30h), the living zebrafish embryo is an ideal system to examine mif and mcp1 cytokine pathways and interactions...
September 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28923369/rapid-identification-and-validation-of-novel-targeted-approaches-for-glioblastoma-a-combined-ex-vivo-in-vivo-pharmaco-omic-model
#2
REVIEW
Ahmad Daher, John de Groot
Tumor heterogeneity is a major factor in glioblastoma's poor response to therapy and seemingly inevitable recurrence. Only two glioblastoma drugs have received Food and Drug Administration approval since 1998, highlighting the urgent need for new therapies. Profiling "omics" analyses have helped characterize glioblastoma molecularly and have thus identified multiple molecular targets for precision medicine. These molecular targets have influenced clinical trial design; many "actionable" mutation-focused trials are underway, but because they have not yet led to therapeutic breakthroughs, new strategies for treating glioblastoma, especially those with a pharmacological functional component, remain in high demand...
September 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28923368/insights-into-the-structural-biology-of-gaucher-disease
#3
REVIEW
Laura Smith, Stephen Mullin, Anthony H V Schapira
Gaucher disease, the most common lysosomal storage disorder, is caused by mutations in the gene encoding the acid-β-glucosidase lysosomal hydrolase enzyme that cleaves glucocerebroside into glucose and ceramide. Reduced enzyme activity and impaired structural stability arise due to >300 known disease-causing mutations. Several of these mutations have also been associated with an increased risk of Parkinson disease (PD). Since the discovery of the acid-β-glucosidase X-ray structure, there have been major advances in our understanding of the structural properties of the protein...
September 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28917641/changes-in-innervation-of-lumbar-motoneurons-and-organization-of-premotor-network-following-training-of-transected-adult-rats
#4
Loubna Khalki, Karina Sadlaoud, Julie Lerond, Jacques-Olivier Coq, Jean-Michel Brezun, Laurent Vinay, Patrice Coulon, Hélène Bras
Rats with complete spinal cord transection (SCT) can recover hindlimb locomotor function under strategies combining exercise training and 5-HT agonist treatment. This recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. To begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (GS) or tibialis anterior (TA) motoneurons (MNs) in SCT rats after a schedule of early exercise training and delayed 5-HT agonist treatment...
September 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28911884/anti-vegf-treatment-improves-neurological-function-in-tumors-of-the-nervous-system
#5
REVIEW
Na Zhang, Jie Chen, Gino Ferraro, Limeng Wu, Meenal Datta, Rakesh K Jain, Scott R Plotkin, Anat Stemmer-Rachamimov, Lei Xu
Research of various diseases of the nervous system has shown that VEGF has direct neuroprotective effects in the central and peripheral nervous systems, and indirect effects on improving neuronal vessel perfusion which leads to nerve protection. In the tumors of the nervous system, VEGF plays a critical role in tumor angiogenesis and tumor progression. The effect of anti-VEGF treatment on nerve protection and function has been recently reported - by normalizing the tumor vasculature, anti-VEGF treatment is able to relieve nerve edema and deliver oxygen more efficiently into the nerve, thus reducing nerve damage and improving nerve function...
September 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28911883/tnf-superfamily-member-april-enhances-midbrain-dopaminergic-axon-growth-and-contributes-to-the-nigrostriatal-projection-in-vivo
#6
Thomas G McWilliams, Laura Howard, Sean Wyatt, Alun M Davies
We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages. The axon growth-enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons...
September 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28893517/differential-effects-of-levodopa-and-apomorphine-on-neuronal-population-oscillations-in-the-cortico-basal-ganglia-loop-circuit-in-vivo-in-experimental-parkinsonism
#7
Johanna Kühn, Jens K Haumesser, Maximilian H Beck, Jennifer Altschüler, Andrea A Kühn, Vadim N Nikulin, Christoph van Riesen
The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28890075/down-regulation-of-dorsal-striatal-%C3%AE-camkii-causes-striatum-related-cognitive-and-synaptic-disorders
#8
Qi Wang, Pengcheng Yin, Bin Yu, Zheng Zhao, Gal Richter-Levin, Lu Yu, Xiaohua Cao
Alpha calcium/calmodulin dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase which is expressed abundantly in dorsal striatum and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, it currently remains unclear whether and how αCaMKII plays a in the striatum-related neural disorders. To address the above issue, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of αCaMKII gene in the dorsal striatum of mice. As a consequence of down-regulation of dorsal striatal αCaMKII expression, we observed defective motor skill learning in accelerating rotarod and response learning in water cross maze...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28882412/a-flavonoid-agonist-of-the-trkb-receptor-for-bdnf-improves-hippocampal-neurogenesis-and-hippocampus-dependent-memory-in-the-ts65dn-mouse-model-of-ds
#9
Fiorenza Stagni, Andrea Giacomini, Sandra Guidi, Marco Emili, Beatrice Uguagliati, Maria Elisa Salvalai, Valeria Bortolotto, Mariagrazia Grilli, Roberto Rimondini, Renata Bartesaghi
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB)...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28882411/prenatal-stress-induced-impairments-of-cognitive-flexibility-and-bidirectional-synaptic-plasticity-are-possibly-associated-with-autophagy-in-adolescent-male-offspring
#10
Hui Zhang, Yingchun Shang, Xi Xiao, Mei Yu, Tao Zhang
Prenatal stress (PS) brings numerous outcomes on offspring, including anxiety, depression-like behavior and other cognitive disorder. In this study, a rat model of PS was established by using restraint stress for 45min three times per day from the 15th to 21st day of pregnancy. Behavioral tests, including open field test (OPT), elevated plus-maze (EPM) and Morris water-maze (MWM), were performed in adolescent male-offspring. The bidirectional synaptic plasticity, including long-term potential (LTP) and depotentiation (DEP), from the hippocampal Schaffer collaterals to CA1 region was subsequently measured...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28867485/mechanisms-of-action-of-cannabidiol-in-adoptively-transferred-experimental-autoimmune-encephalomyelitis
#11
Coral González-García, Irene Moreno Torres, Ruth García-Hernández, Lucía Campos-Ruíz, Luis Rodríguez Esparragoza, María José Coronado, Aranzazu García Grande, Antonio García-Merino, Antonio J Sánchez López
Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG35-55 and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice...
September 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28865993/genetic-neutrophil-deficiency-ameliorates-cerebral-ischemia-reperfusion-injury
#12
Ryan A Frieler, Yutein Chung, Carolyn G Ahlers, George Gheordunescu, Jianrui Song, Thomas M Vigil, Yatrik M Shah, Richard M Mortensen
Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Myeloid Mcl1 knockout mice were subjected to transient middle cerebral artery occlusion and infarct size was assessed by MRI after 24h reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry. We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1(+/+): 78...
August 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28859862/the-promise-of-signal-transduction-in-genetically-driven-sarcomas-of-the-nerve
#13
REVIEW
AeRang Kim, Christine A Pratilas
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome. Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas arising from peripheral nerve sheaths, and the most commonly lethal feature associated with NF1. The hallmark of NF1 and NF1-related MPNST is the loss of neurofibromin expression. Loss of neurofibromin is considered a tumor-promoting event, and leads to constitutive activation of RAS and its downstream effectors. However, RAS activation alone is not sufficient for MPNST formation, and additional tumor suppressors and signaling pathways have been implicated in tumorigenesis of MPNST...
August 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28851597/intraspinal-tlr4-activation-promotes-iron-storage-but-does-not-protect-neurons-or-oligodendrocytes-from-progressive-iron-mediated-damage
#14
Evan Z Goldstein, Jamie S Church, Nicole Pukos, Manoj K Gottipati, Phillip G Popovich, Dana M McTigue
Iron is essential for basic cellular functions but in excess is highly toxic. For this reason, free iron and iron storage are controlled in the periphery by elaborate regulatory mechanisms. In contrast, iron regulation in the central nervous system (CNS) is not well defined. Given that excess iron is present after trauma, hemorrhagic stroke and neurodegeneration, understanding normal iron regulation and promoting iron uptake in CNS pathology is crucial. Peripherally, toll-like receptor 4 (TLR4) activation promotes iron sequestration by macrophages...
August 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28844606/ampk-activation-role-in-the-signaling-pathways-of-neuroinflammation-and-neurodegeneration
#15
REVIEW
Christina Alves Peixoto, Wilma Helena de Oliveira, Shyrlene Meiry da Racho Araújo, Ana Karolina Santana Nunes
Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status and has been reported to be involved in chronic inflammatory disorders. AMPK is expressed in immune cells, such as dendritic cells, macrophages, lymphocytes and neutrophils, and is an important regulator of inflammatory responses through the regulation of complex signaling networks in part by inhibiting downstream cascade pathways, such as nuclear factor kB, which is a key regulator of innate immunity and inflammation, as well as acting as a negative regulator of toll-like receptors...
August 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28843543/microglia-and-macrophages-differ-in-their-inflammatory-profile-after-permanent-brain-ischemia
#16
REVIEW
Juan G Zarruk, Andrew D Greenhalgh, Samuel David
We studied the expression of pro- and anti-inflammatory molecules in microglia and infiltrating monocyte-derived macrophages after permanent Middle Cerebral Artery Occlusion (pMCAO). LysM-EGFP knock-in mice were used to distinguish between these two cell types, as peripheral myeloid cells are LysM-EGFP(+), while microglia are not. This was confirmed with P2ry12 (a microglial specific marker), Iba-1 and EGFP immunostaining. The peak of LysM-EGFP(+) myeloid cell infiltration was 72h post-ischemia, and were distributed evenly in the lesion core, surrounded by a dense region of microglia...
August 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28843542/effects-of-gaba-microinjection-into-dorsal-raphe-nucleus-on-behavior-and-activity-of-lateral-habenular-neurons-in-mice
#17
Jinyu Xiao, Meiying Song, Fengdan Li, Xiaofeng Liu, Alinur Anwar, Hua Zhao
The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced behavioral changes have not been investigated...
August 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28830762/contribution-of-amygdala-crf-neurons-to-chronic-pain
#18
Matthew Andreoli, Tanvi Marketkar, Eugene Dimitrov
We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord...
August 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28823823/immunization-of-mice-with-lrp4-induces-myasthenia-similar-to-musk-associated-myasthenia-gravis
#19
Shuuichi Mori, Norio Motohashi, Rumi Takashima, Masahiko Kishi, Hiroshi Nishimune, Kazuhiro Shigemoto
Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice...
August 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28822839/decreased-surface-expression-of-the-%C3%AE-subunit-of-the-gabaa-receptor-contributes-to-reduced-tonic-inhibition-in-dentate-granule-cells-in-a-mouse-model-of-fragile-x-syndrome
#20
Nianhui Zhang, Zechun Peng, Xiaoping Tong, A Kerstin Lindemeyer, Yliana Cetina, Christine S Huang, Richard W Olsen, Thomas S Otis, Carolyn R Houser
While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABAA receptors (GABAARs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABAAR, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS...
August 16, 2017: Experimental Neurology
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