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Experimental Neurology

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https://www.readbyqxmd.com/read/28434869/worms-on-the-spectrum-c-elegans-models-in-autism-research
#1
REVIEW
Kathrin Schmeisser, J Alex Parker
The small non-parasitic nematode Caenorhabditis elegans is widely used in neuroscience thanks to its well-understood development and lineage of the nervous system. Furthermore, C. elegans has been used to model many human developmental and neurological conditions to better understand disease mechanisms and identify potential therapeutic strategies. Autism spectrum disorder (ASD) is the most prevalent of all neurodevelopmental disorders, and the C. elegans system may provide opportunities to learn more about this complex disorder...
April 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28433644/supraspinal-respiratory-plasticity-following-acute-cervical-spinal-cord-injury
#2
Tatiana Bezdudnaya, Vitaliy Marchenko, Lyandysha V Zholudeva, Victoria M Spruance, Michael A Lane
Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks...
April 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28431876/role-of-the-locus-coeruleus-catecholaminergic-neurons-in-the-chemosensory-control-of-breathing-in-a-parkinson-s-disease-model
#3
Luiz M Oliveira, Marina Tuppy, Thiago S Moreira, Ana C Takakura
A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40days after PD-induction. The functional deficiency is restored 60days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before, and then 40 and 60days after bilateral 6-OHDA (24μg/μL) or vehicle injections into the LC in control or PD-induced male Wistar rats...
April 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28427858/mice-with-conditional-neurod1-knockout-display-reduced-aberrant-hippocampal-neurogenesis-but-no-change-in-epileptic-seizures
#4
Rebecca Brulet, Jingfei Zhu, Mahafuza Aktar, Jenny Hsieh, Kyung-Ok Cho
Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiation and maturation of adult-generated neurons in the hippocampus...
April 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28412220/inflammation-induced-glua1-trafficking-and-membrane-insertion-of-ca-2-permeable-ampa-receptors-in-dorsal-horn-neurons-is-dependent-on-spinal-tumor-necrosis-factor-pi3-kinase-and-protein-kinase-a
#5
G Wigerblad, J R Huie, H Z Yin, M Leinders, R A Pritchard, F J Koehrn, W-H Xiao, G J Bennett, R L Huganir, A R Ferguson, J H Weiss, C I Svensson, L S Sorkin
Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls...
April 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28411125/hypersociability-in-the-angelman-syndrome-mouse-model
#6
David C Stoppel, Matthew P Anderson
Deletions and reciprocal triplications of the human chromosomal 15q11-13 region cause two distinct neurodevelopmental disorders. Maternally-derived deletions or inactivating mutations of UBE3A, a 15q11-13 gene expressed exclusively from the maternal allele in neurons, cause Angelman syndrome, characterized by intellectual disability, motor deficits, seizures, and a characteristic increased social smiling, laughing, and eye contact. Conversely, maternally-derived triplications of 15q11-13 cause a behavioral disorder on the autism spectrum with clinical features that include decreased sociability that we recently reconstituted in mice with Ube3a alone...
April 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28392281/human-stem-cell-modeling-in-neurofibromatosis-type-1-nf1
#7
REVIEW
Michelle L Wegscheid, Corina Anastasaki, David H Gutmann
The future of precision medicine is heavily reliant on the use of human tissues to identify the key determinants that account for differences between individuals with the same disorder. This need is exemplified by the neurofibromatosis type 1 (NF1) neurogenetic condition. As such, individuals with NF1 are born with a germline mutation in the NF1 gene, but may develop numerous distinct neurological problems, ranging from autism and attention deficit to brain and peripheral nerve sheath tumors. Coupled with accurate preclinical mouse models, the availability of NF1 patient-derived induced pluripotent stem cells (iPSCs) provides new opportunities to define the critical factors that underlie NF1-associated nervous system disease pathogenesis and progression...
April 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28373025/early-life-febrile-seizures-worsen-adult-phenotypes-in-scn1a-mutants
#8
Stacey B B Dutton, Karoni Dutt, Ligia A Papale, Sandra Helmers, Alan L Goldin, Andrew Escayg
Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Nav1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS). Patients with SCN1A mutations often experience prolonged early-life febrile seizures (FSs), raising the possibility that these events may influence epileptogenesis and lead to more severe adult phenotypes. To test this hypothesis, we subjected 21-23-day-old mice expressing the human SCN1A GEFS+ mutation R1648H to prolonged hyperthermia, and then examined seizure and behavioral phenotypes during adulthood...
April 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28373024/a-rapid-chemical-genetic-screen-utilizing-impaired-movement-phenotypes-in-c-elegans-input-into-genetics-of-neurodevelopmental-disorders
#9
Kathrin Schmeisser, Yasmin Fardghassemi, J Alex Parker
Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder with a constantly increasing prevalence. Model organisms may be tools to identify underlying cellular and molecular mechanisms, as well as aid the discovery and development of novel therapeutic approaches. A simple animal such as the nematode Caenorhabditis elegans may provide insights into the extreme complexity of ASD genetics. Despite its potential, using C. elegans in ASD research is a controversial approach and has not yet been used extensively in this context...
April 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28366471/phosphodiesterase-4-inhibition-restored-hippocampal-long-term-potentiation-after-primary-blast
#10
Edward W Vogel, Fatima N Morales, David F Meaney, Cameron R Bass, Barclay Morrison
Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) and that primary blast affects key proteins governing LTP...
March 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28366470/ascending-projections-of-nociceptive-neurons-from-trigeminal-subnucleus-caudalis-a-population-approach
#11
Hiroto Saito, Ayano Katagiri, Shinji Okada, Lou Mikuzuki, Asako Kubo, Tatsuro Suzuki, Kinuyo Ohara, Jun Lee, Nobuhito Gionhaku, Toshimitsu Iinuma, David A Bereiter, Koichi Iwata
Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1)...
March 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28365474/tdag8-activation-attenuates-cerebral-ischaemia-reperfusion-injury-via-akt-signalling-in-rats
#12
X D Ma, L H Hang, D H Shao, W W Shu, X L Hu, H Luo
BACKGROUND: T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. METHODS: We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression...
March 30, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28365473/pioglitazone-treatment-following-spinal-cord-injury-maintains-acute-mitochondrial-integrity-and-increases-chronic-tissue-sparing-and-functional-recovery
#13
Samir P Patel, David H Cox, Jenna L Gollihue, William M Bailey, Werner J Geldenhuys, John C Gensel, Patrick G Sullivan, Alexander G Rabchevsky
Pioglitazone is an FDA-approved PPAR-γ agonist drug used to treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice...
March 30, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28359739/2-4-dnp-improves-motor-function-preserves-medium-spiny-neuronal-identity-and-reduces-oxidative-stress-in-a-mouse-model-of-huntington-s-disease
#14
Bin Wu, Mali Jiang, Qi Peng, Gang Li, Zhipeng Hou, Ginger L Milne, Susumu Mori, Robert Alonso, John G Geisler, Wenzhen Duan
Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the gene huntingtin. There is no treatment to prevent or delay the disease course of HD currently. Oxidative stress and mitochondrial dysfunction have emerged as key determinants of the disease progression in HD. Therefore, counteracting mutant huntingtin (mHtt)-induced oxidative stress and mitochondrial dysfunction appears as a new approach to treat this devastating disease. Interestingly, mild mitochondrial uncoupling improves neuronal resistance to stress and facilitates neuronal survival...
March 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28359740/bilateral-tactile-hypersensitivity-and-neuroimmune-responses-after-spared-nerve-injury-in-mice-lacking-vasoactive-intestinal-peptide
#15
Alessandro Gallo, Marjolein Leerink, Benoît Michot, Eman Ahmed, Patrice Forget, André Mouraux, Emmanuel Hermans, Ronald Deumens
Vasoactive intestinal peptide (VIP) is one of the neuropeptides showing the strongest up-regulation in the nociceptive pathway after peripheral nerve injury and has been proposed to support neuropathic pain. Nevertheless, the story may be more complicated considering the known suppressive effects of the peptide on the immune reactivity of microglial cells, which have been heavily implicated in the onset and maintenance of pain after nerve injury. We here used mice deficient in VIP and the model of spared nerve injury, characterized by persistent tactile hypersensitivity...
March 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28351750/a-longitudinal-dti-and-histological-study-of-the-spinal-cord-reveals-early-pathological-alterations-in-g93a-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Stefania Marcuzzo, Silvia Bonanno, Matteo Figini, Alessandro Scotti, Ileana Zucca, Ludovico Minati, Nilo Riva, Teuta Domi, Andrea Fossaghi, Angelo Quattrini, Barbara Galbardi, Sara D'Alessandro, Maria Grazia Bruzzone, José Manuel García-Verdugo, Victoria Moreno-Manzano, Renato Mantegazza, Pia Bernasconi
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 ALS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology...
March 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28347764/bdnf-is-required-for-taste-axon-regeneration-following-unilateral-chorda-tympani-nerve-section
#17
Lingbin Meng, Tao Huang, Chengsan Sun, David L Hill, Robin Krimm
Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice...
March 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28347765/spinal-cord-injury-in-hypertonic-newborns-after-antenatal-hypoxia-ischemia-in-a-rabbit-model-of-cerebral-palsy
#18
Alexander Drobyshevsky, Katharina A Quinlan
While antenatal hypoxia-ischemia (H-I) is a well-established cause of brain injury, the effects of H-I on the spinal cord remain undefined. This study examined whether hypertonia in rabbits was accompanied by changes in spinal architecture. Rabbit dams underwent global fetal H-I at embryonic day 25 for 40min. High resolution diffusion tensor imaging was performed on fixed neonatal CNS. Fractional anisotropy (FA) and regional volumetric measurements were compared between kits with and without hypertonia after H-I and sham controls using Tract Based Spatial Statistics...
March 24, 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
#19
Samantha M Meadows, Nicole E 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 23, 2017: Experimental Neurology
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
#20
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
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