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D O Setter, E M Runge, N D Schartz, F M Kennedy, B L Brown, K P McMillan, W M Miller, K M Shah, M M Haulcomb, V M Sanders, K J Jones
When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2(-/-)) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2(-/-) mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2(-/-) mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA...
October 10, 2017: Brain, Behavior, and Immunity
Warley Carvalho da Silva Martins, Lucas Alverne Freitas de Albuquerque, Gervásio Teles Cardoso de Carvalho, Jules Carlos Dourado, Marcos Dellaretti, Atos Alves de Sousa
BACKGROUND: Bilateral hemifacial spasm (BHFS) is a rare neurological syndrome whose diagnosis depends on excluding other facial dyskinesias. We present a case of BHFS along with a literature review. METHODS: A 64-year-old white, hypertense male reported involuntary left hemiface contractions in 2001 (aged 50). In 2007, right hemifacial symptoms appeared, without spasm remission during sleep. Botulinum toxin type A application produced partial temporary improvement...
2017: Surgical Neurology International
Michael George Zaki Ghali
The pontomedullary respiratory network generates the respiratory pattern and relays it to bulbar and spinal respiratory motor outputs. The phrenic motor system controlling diaphragm contraction receives and processes descending commands to produce orderly, synchronous, and cycle-to-cycle-reproducible spatiotemporal firing. Multiple investigators have studied PhMNs in an attempt to shed light on local mechanisms underlying phrenic pattern formation. We recorded PhMNs in unanesthetized, decerebrate rats and related their activity to simultaneous phrenic nerve (PhN) activity by creating a time-frequency representation of PhMN-PhN power and coherence...
October 11, 2017: Journal of Neurophysiology
Sebastian Rademacher, Bert M Verheijen, Niko Hensel, Miriam Peters, Gamze Bora, Gudrun Brandes, Renata Vieira de Sá, Natascha Heidrich, Silke Fischer, Hella Brinkmann, W Ludo van der Pol, Brunhilde Wirth, R Jeroen Pasterkamp, Peter Claus
Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent...
October 15, 2017: Human Molecular Genetics
Michiyo Suzuki, Yuya Hattori, Tetsuya Sakashita, Yuichiro Yokota, Yasuhiko Kobayashi, Tomoo Funayama
Radiation may affect essential functions and behaviors such as locomotion, feeding, learning and memory. Although whole-body irradiation has been shown to reduce motility in the nematode Caenorhabditis elegans, the detailed mechanism responsible for this effect remains unknown. Targeted irradiation of the nerve ring responsible for sensory integration and information processing would allow us to determine whether the reduction of motility following whole-body irradiation reflects effects on the central nervous system or on the muscle cells themselves...
August 30, 2017: Journal of Radiation Research
Anuradha Tennakoon, Viythia Katharesan, Ian P Johnson
Neuroinflammation is linked to healthy ageing, but its role in the development of age-related neurodegenerative diseases is unclear. In this pilot study we used a multiplex assay approach to compare 27 cytokines in 6 young adult and 6 ageing control brainstems with those in 6 MND brainstems. We report that healthy ageing is associated with significantly increased brainstem levels of IL-1β, IP-10 and MIP-1β which co-localise immunocytochemically to astrocytes. MND brainstem is also characterised by a general increase in both pro- and anti-cytokine levels, but fails to show the expected age-related increase in MIP-1β and IP-10...
October 15, 2017: Journal of the Neurological Sciences
Vanessa Plantier, Frédéric Brocard
After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I NaP), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl(-)) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium channels, the upregulation of I NaP and spasticity following SCI...
June 2017: Médecine Sciences: M/S
Riccardo De Santis, Laura Santini, Alessio Colantoni, Giovanna Peruzzi, Valeria de Turris, Vincenzo Alfano, Irene Bozzoni, Alessandro Rosa
The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases...
September 28, 2017: Stem Cell Reports
Lena Saal-Bauernschubert, Michael Briese, Michael Sendtner
In highly polarized cells such as neurons, most RNA molecules are not randomly distributed but sorted into different compartments. So far, methods to analyze the transcriptome in distinct subcellular compartments are not well established. Here, we first describe the culturing of primary motoneurons in compartmentalized chambers to separate the axons from the somatodendritic compartment. Second, we introduce a method for whole transcriptome amplification followed by high-throughput sequencing to analyze the RNA composition of these two different compartments in neuronal cells...
2017: Methods in Molecular Biology
Dimitrios Kadas, Aylin Klein, Niklas Krick, Jason W Worrell, Stefanie Ryglewski, Carsten Duch
Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Cav1 homolog) L-type like calcium channels localize to both, the somatodendritic and the axonal compartment of larval crawling motoneurons...
October 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Danilo B Medinas, Vicente Valenzuela, Claudio Hetz
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motoneurons in the brain and spinal cord leading to paralysis and death. Although the etiology of ALS remains poorly understood, abnormal protein aggregation and altered proteostasis are common features of sporadic and familial ALS forms. The proteostasis network is decomposed into different modules highly conserved across species and comprehends a collection of mechanisms related to protein synthesis, folding, trafficking, secretion and degradation that is distributed in different compartments inside the cell...
October 1, 2017: Human Molecular Genetics
Preston T J A Williams, Yu-Qiu Jiang, John H Martin
In maturity, motor skills depend on the corticospinal tract (CST) and brainstem pathways that together synapse on interneurons and motoneurons in the spinal cord. Descending signals to spinal neurons that mediate voluntary control can be distinguished from peripheral sensory signals, primarily for feedback control. These motor system circuits depend initially on developmental genetic mechanisms to establish their connections and neural activity- and use-dependent synaptic refinement during the early postnatal period to enable motor skills to develop...
October 3, 2017: Developmental Medicine and Child Neurology
David Schoppik, Isaac H Bianco, David A Prober, Adam D Douglass, Drew N Robson, Jennifer M B Li, Joel S F Greenwood, Edward Soucy, Florian Engert, Alexander F Schier
Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations -- such as asymmetric connectivity -- to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically-defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish...
September 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Martha Canto-Bustos, Emanuel Loeza-Alcocer, Carlos A Cuellar, Paulina Osuna, David Elias-Viñas, Vinicio Granados-Soto, Elías Manjarrez, Ricardo Felix, Rodolfo Delgado-Lezama
Motoneurons, the final common path of the Central Nervous System (CNS), are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT) positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents...
2017: Frontiers in Cellular Neuroscience
Tomohiro Ohgomori, Ryo Yamasaki, Jun-Ichi Kira, Shozo Jinno
Chronic administration of 3,3'-iminodipropionitrile (IDPN) causes axonal impairment. Although controversy still remains, it has been suggested that IDPN intoxication mimics the axonopathy of amyotrophic lateral sclerosis (ALS). Interestingly, recent studies including our own showed that signal transducer and activator of transcription 3 (STAT3) in spinal α-motoneurons was activated in both IDPN-treated mice and SOD1 (G93A) mice, a genetic model of familial ALS. Because activation of STAT3 occurs in response to various stimuli, such as axonal injury, ischemia, and excessive glutamate, here we focused on a potential link between phosphorylated STAT3 (pSTAT3, an active form) and vesicular glutamate transporter 2 (VGluT2, a regulator of glutamate storage and release) in IDPN-treated mice and SOD1 (G93A) mice...
September 30, 2017: Neurotoxicity Research
Sergio H Duenas-Jimenez, Luis Castillo Hernandez, Braniff de la Torre Valdovinos, Gerardo Mendizabal Ruiz, Judith M Duenas Jimenez, Viviana Ramirez Abundis, Irene Guadalupe Aguilar Garcia
In brain cortex-ablated cats (BCAC), hind limb motoneurons activity patterns were studied during fictive locomotion (FL) or fictive scratching (FS) induced by pinna stimulation. In order to study motoneurons excitability: heteronymous monosynaptic reflex (HeMR), intracellular recording, and individual Ia afferent fiber antidromic activity (AA) were analyzed. The intraspinal cord microinjections of serotonin or glutamic acid effects were made to study their influence in FL or FS During FS, HeMR amplitude in extensor and bifunctional motoneurons increased prior to or during the respective electroneurogram (ENG)...
September 2017: Physiological Reports
Jason M Guest, Mythreya M Seetharama, Elizabeth S Wendel, Peter L Strick, Marcel Oberlaender
The rodent facial nucleus (FN) comprises motoneurons (MNs) that control the facial musculature. In the lateral part of the FN, populations of vibrissal motoneurons (vMNs) innervate two groups of muscles that generate movements of the whiskers. Vibrissal MNs thus represent the terminal point of the neuronal networks that generate rhythmic whisking during exploratory behaviors and that modify whisker movements based on sensory-motor feedback during tactile-based perception. Here, we combined retrograde tracer injections into whisker-specific muscles, with large-scale immunohistochemistry and digital reconstructions to generate an average model of the rat FN...
September 27, 2017: Neuroscience
Mareike Floegel, Christian Alexander Kell
Both hemispheres contribute to motor control beyond the innervation of the contralateral alpha motoneurons. The left hemisphere has been associated with higher-order aspects of motor control like sequencing and temporal processing, the right hemisphere with the transformation of visual information to guide movements in space. In the visuomotor context, empirical evidence regarding the latter has been limited though the right hemisphere's specialization for visuospatial processing is well-documented in perceptual tasks...
2017: PloS One
Mathieu Bourguignon, Harri Piitulainen, Eero Smeds, Guangyu Zhou, Veikko Jousmäki, Riitta Hari
To gain fundamental knowledge on how the brain controls motor actions, we studied in detail the interplay between MEG signals from the primary sensorimotor (SM1) cortex and the contraction force of 17 healthy adult humans (7 females).SM1 activity was coherent at ∼20-Hz with surface electromyogram (as already extensively reported) but also with contraction force. In both cases the effective coupling was dominant in the efferent direction. Across subjects, the level of ∼20-Hz coherence between cortex and periphery positively correlated with the "burstiness" of ∼20-Hz SM1 (Pearson r ≈ 0...
September 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Maria Meyer, Laura I Garay, María Sol Kruse, Agustina Lara, Gisella Gargiulo-Monachelli, Michael Schumacher, Rachida Guennoun, Hector Coirini, Alejandro F De Nicola, Maria Claudia Gonzalez Deniselle
Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by progressive death of motoneurons. The Wobbler (WR) mouse is a preclinical model sharing neuropathological similarities with human ALS. We have shown that progesterone (PROG) prevents the progression of motoneuron degeneration. We now studied if allopregnanolone (ALLO), a reduced metabolite of PROG endowed with gabaergic activity, also prevents WR neuropathology. Sixty-day old WRs remained untreated or received two steroid treatment regimens in order to evaluate the response of several parameters during early or prolonged steroid administration...
September 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
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