Motor Neurons: • Alpha Motor Neurons Motor Unit • Gamma Motor Neurons Muscle Spindle • Interneurons , Renshaw Cells
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Primary Lateral Sclerosis, Upper Motor Neuron Dominant Amyotrophic Lateral Sclerosis, and Hereditary Spastic Paraplegia
brain sciences Review Upper Motor Neuron Disorders: Primary Lateral Sclerosis, Upper Motor Neuron Dominant Amyotrophic Lateral Sclerosis, and Hereditary Spastic Paraplegia Timothy Fullam and Jeffrey Statland * Department of Neurology, University of Kansas Medical Center, Kansas, KS 66160, USA; [email protected] * Correspondence: [email protected] Abstract: Following the exclusion of potentially reversible causes, the differential for those patients presenting with a predominant upper motor neuron syndrome includes primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), or upper motor neuron dominant ALS (UMNdALS). Differentiation of these disorders in the early phases of disease remains challenging. While no single clinical or diagnostic tests is specific, there are several developing biomarkers and neuroimaging technologies which may help distinguish PLS from HSP and UMNdALS. Recent consensus diagnostic criteria and use of evolving technologies will allow more precise delineation of PLS from other upper motor neuron disorders and aid in the targeting of potentially disease-modifying therapeutics. Keywords: primary lateral sclerosis; amyotrophic lateral sclerosis; hereditary spastic paraplegia Citation: Fullam, T.; Statland, J. Upper Motor Neuron Disorders: Primary Lateral Sclerosis, Upper 1. Introduction Motor Neuron Dominant Jean-Martin Charcot (1825–1893) and Wilhelm Erb (1840–1921) are credited with first Amyotrophic Lateral Sclerosis, and describing a distinct clinical syndrome of upper motor neuron (UMN) tract degeneration in Hereditary Spastic Paraplegia. Brain isolation with symptoms including spasticity, hyperreflexia, and mild weakness [1,2]. Many Sci. 2021, 11, 611. https:// of the earliest described cases included cases of hereditary spastic paraplegia, amyotrophic doi.org/10.3390/brainsci11050611 lateral sclerosis, and underrecognized structural, infectious, or inflammatory etiologies for upper motor neuron dysfunction which have since become routinely diagnosed with the Academic Editors: P. -
Neural Control of Movement: Motor Neuron Subtypes, Proprioception and Recurrent Inhibition
List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Enjin A, Rabe N, Nakanishi ST, Vallstedt A, Gezelius H, Mem- ic F, Lind M, Hjalt T, Tourtellotte WG, Bruder C, Eichele G, Whelan PJ, Kullander K (2010) Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as mark- ers for fast motor neurons and partition cells. J Comp Neurol 518:2284-2304. II Wootz H, Enjin A, Wallen-Mackenzie Å, Lindholm D, Kul- lander K (2010) Reduced VGLUT2 expression increases motor neuron viability in Sod1G93A mice. Neurobiol Dis 37:58-66 III Enjin A, Leao KE, Mikulovic S, Le Merre P, Tourtellotte WG, Kullander K. 5-ht1d marks gamma motor neurons and regulates development of sensorimotor connections Manuscript IV Enjin A, Leao KE, Eriksson A, Larhammar M, Gezelius H, Lamotte d’Incamps B, Nagaraja C, Kullander K. Development of spinal motor circuits in the absence of VIAAT-mediated Renshaw cell signaling Manuscript Reprints were made with permission from the respective publishers. Cover illustration Carousel by Sasha Svensson Contents Introduction.....................................................................................................9 Background...................................................................................................11 Neural control of movement.....................................................................11 The motor neuron.....................................................................................12 Organization -
Electromagnetic Field and TGF-Β Enhance the Compensatory
www.nature.com/scientificreports OPEN Electromagnetic feld and TGF‑β enhance the compensatory plasticity after sensory nerve injury in cockroach Periplaneta americana Milena Jankowska1, Angelika Klimek1, Chiara Valsecchi2, Maria Stankiewicz1, Joanna Wyszkowska1* & Justyna Rogalska1 Recovery of function after sensory nerves injury involves compensatory plasticity, which can be observed in invertebrates. The aim of the study was the evaluation of compensatory plasticity in the cockroach (Periplaneta americana) nervous system after the sensory nerve injury and assessment of the efect of electromagnetic feld exposure (EMF, 50 Hz, 7 mT) and TGF‑β on this process. The bioelectrical activities of nerves (pre‑and post‑synaptic parts of the sensory path) were recorded under wind stimulation of the cerci before and after right cercus ablation and in insects exposed to EMF and treated with TGF‑β. Ablation of the right cercus caused an increase of activity of the left presynaptic part of the sensory path. Exposure to EMF and TGF‑β induced an increase of activity in both parts of the sensory path. This suggests strengthening efects of EMF and TGF‑β on the insect ability to recognize stimuli after one cercus ablation. Data from locomotor tests proved electrophysiological results. The takeover of the function of one cercus by the second one proves the existence of compensatory plasticity in the cockroach escape system, which makes it a good model for studying compensatory plasticity. We recommend further research on EMF as a useful factor in neurorehabilitation. Injuries in the nervous system caused by acute trauma, neurodegenerative diseases or even old age are hard to reverse and represent an enormous challenge for modern medicine. -
The Muscular System
THE MUSCULAR SYSTEM COMPILED BY HOWIE BAUM 1 Muscles make up the bulk of the body and account for 1/3 of its weight.!! Blood vessels and nerves run to every muscle, helping control and regulate each muscle’s function. The muscular system creates body heat and also moves the: Bones of the Skeletal system Food through Digestive system Blood through the Circulatory system Fluids through the Excretory system MUSCLE TISSUE The body has 3 main types of muscle tissue 1) Skeletal, 2) Smooth, and 3) Cardiac SKELETAL MUSCLE SMOOTH MUSCLE CARDIAC MUSCLE Skeletal muscles attach to and move bones by contracting and relaxing in response to voluntary messages from the nervous system. Skeletal muscle tissue is composed of long cells called muscle fibers that have a striated appearance. Muscle fibers are organized into bundles supplied by blood vessels and innervated by motor neurons. Muscle structure Skeletal (striated or voluntary) muscle consists of densely packed groups of hugely elongated cells known as myofibers. These are grouped into bundles (fascicles). A typical myofiber is 2–3 centimeters ( 3/4–1 1/5 in) long and 0.05millimeters (1/500 inch) in diameter and is composed of narrower structures – myofibrils. These contain thick and thin myofilaments made up mainly of the proteins actin and myosin. Numerous capillaries keep the muscle supplied with the oxygen and glucose needed to fuel contraction. Skeletal Muscles • Skeletal muscles attach to bones by tendons (connective tissue) and enable movement. • Skeletal muscles are mostly voluntary Feel the back of your ankle to feel your Achilles tendon - the largest tendon in your body. -
ALS and Other Motor Neuron Diseases Can Represent Diagnostic Challenges
Review Article Address correspondence to Dr Ezgi Tiryaki, Hennepin ALS and Other Motor County Medical Center, Department of Neurology, 701 Park Avenue P5-200, Neuron Diseases Minneapolis, MN 55415, [email protected]. Ezgi Tiryaki, MD; Holli A. Horak, MD, FAAN Relationship Disclosure: Dr Tiryaki’s institution receives support from The ALS Association. Dr Horak’s ABSTRACT institution receives a grant from the Centers for Disease Purpose of Review: This review describes the most common motor neuron disease, Control and Prevention. ALS. It discusses the diagnosis and evaluation of ALS and the current understanding of its Unlabeled Use of pathophysiology, including new genetic underpinnings of the disease. This article also Products/Investigational covers other motor neuron diseases, reviews how to distinguish them from ALS, and Use Disclosure: Drs Tiryaki and Horak discuss discusses their pathophysiology. the unlabeled use of various Recent Findings: In this article, the spectrum of cognitive involvement in ALS, new concepts drugs for the symptomatic about protein synthesis pathology in the etiology of ALS, and new genetic associations will be management of ALS. * 2014, American Academy covered. This concept has changed over the past 3 to 4 years with the discovery of new of Neurology. genes and genetic processes that may trigger the disease. As of 2014, two-thirds of familial ALS and 10% of sporadic ALS can be explained by genetics. TAR DNA binding protein 43 kDa (TDP-43), for instance, has been shown to cause frontotemporal dementia as well as some cases of familial ALS, and is associated with frontotemporal dysfunction in ALS. Summary: The anterior horn cells control all voluntary movement: motor activity, res- piratory, speech, and swallowing functions are dependent upon signals from the anterior horn cells. -
(7E) Powerpoint Lecture Outline Chapter 8: Control of Movement
Carlson (7e) PowerPoint Lecture Outline Chapter 8: Control of Movement This multimedia product and its contents are protected under copyright law. The following are prohibited by law: •any public performance or display, including transmission of any image over a network; •preparation of any derivative work, including extraction, in whole or in part, of any images; •any rental, lease, or lending of the program. Copyright 2001 by Allyn & Bacon Skeletal Muscle n Movements of our body are accomplished by contraction of the skeletal muscles l Flexion: contraction of a flexor muscle draws in a limb l Extension: contraction of extensor muscle n Skeletal muscle fibers have a striated appearance n Skeletal muscle is composed of two fiber types: l Extrafusal: innervated by alpha-motoneurons from the spinal cord: exert force l Intrafusal: sensory fibers that detect stretch of the muscle u Afferent fibers: report length of intrafusal: when stretched, the fibers stimulate the alpha-neuron that innervates the muscle fiber: maintains muscle tone u Efferent fibers: contraction adjusts sensitivity of afferent fibers. 8.2 Copyright 2001 by Allyn & Bacon Skeletal Muscle Anatomy n Each muscle fiber consists of a bundle of myofibrils l Each myofibril is made up of overlapping strands of actin and myosin l During a muscle twitch, the myosin filaments move relative to the actin filaments, thereby shortening the muscle fiber 8.3 Copyright 2001 by Allyn & Bacon Neuromuscular Junction n The neuromuscular junction is the synapse formed between an alpha motor neuron -
A System for Studying Mechanisms of Neuromuscular Junction Development and Maintenance Valérie Vilmont1,‡, Bruno Cadot1, Gilles Ouanounou2 and Edgar R
© 2016. Published by The Company of Biologists Ltd | Development (2016) 143, 2464-2477 doi:10.1242/dev.130278 TECHNIQUES AND RESOURCES RESEARCH ARTICLE A system for studying mechanisms of neuromuscular junction development and maintenance Valérie Vilmont1,‡, Bruno Cadot1, Gilles Ouanounou2 and Edgar R. Gomes1,3,*,‡ ABSTRACT different animal models and cell lines (Chen et al., 2014; Corti et al., The neuromuscular junction (NMJ), a cellular synapse between a 2012; Lenzi et al., 2015) with the hope of recapitulating some motor neuron and a skeletal muscle fiber, enables the translation of features of neuromuscular diseases and understanding the triggers chemical cues into physical activity. The development of this special of one of their common hallmarks: the disruption of the structure has been subject to numerous investigations, but its neuromuscular junction (NMJ). The NMJ is one of the most complexity renders in vivo studies particularly difficult to perform. studied synapses. It is formed of three key elements: the lower motor In vitro modeling of the neuromuscular junction represents a powerful neuron (the pre-synaptic compartment), the skeletal muscle (the tool to delineate fully the fine tuning of events that lead to subcellular post-synaptic compartment) and the Schwann cell (Sanes and specialization at the pre-synaptic and post-synaptic sites. Here, we Lichtman, 1999). The NMJ is formed in a step-wise manner describe a novel heterologous co-culture in vitro method using rat following a series of cues involving these three cellular components spinal cord explants with dorsal root ganglia and murine primary and its role is basically to ensure the skeletal muscle functionality. -
Evidence for the Nonmuscle Nature of The" Myofibroblast" of Granulation Tissue and Hypertropic Scar. an Immunofluorescence Study
American Journal of Pathology, Vol. 130, No. 2, February 1988 Copyright i American Association of Pathologists Evidencefor the Nonmuscle Nature ofthe "Myofibroblast" ofGranulation Tissue and Hypertropic Scar An Immunofluorescence Study ROBERT J. EDDY, BSc, JANE A. PETRO, MD, From the Department ofAnatomy, the Department ofSurgery, and JAMES J. TOMASEK, PhD Division ofPlastic and Reconstructive Surgery, and the Department of Orthopaedic Surgery, New York Medical College, Valhalla, New York Contraction is an important phenomenon in wound cell-matrix attachment in smooth muscle and non- repair and hypertrophic scarring. Studies indicate that muscle cells, respectively. Myofibroblasts can be iden- wound contraction involves a specialized cell known as tified by their intense staining of actin bundles with the myofibroblast, which has morphologic character- either anti-actin antibody or NBD-phallacidin. Myofi- istics of both smooth muscle and fibroblastic cells. In broblasts in all tissues stained for nonmuscle but not order to better characterize the myofibroblast, the au- smooth muscle myosin. In addition, nonmuscle myo- thors have examined its cytoskeleton and surrounding sin was localized as intracellular fibrils, which suggests extracellular matrix (ECM) in human burn granula- their similarity to stress fibers in cultured fibroblasts. tion tissue, human hypertrophic scar, and rat granula- The ECM around myofibroblasts stains intensely for tion tissue by indirect immunofluorescence. Primary fibronectin but lacks laminin, which suggests that a antibodies used in this study were directed against 1) true basal lamina is not present. The immunocytoche- smooth muscle myosin and 2) nonmuscle myosin, mical findings suggest that the myofibroblast is a spe- components ofthe cytoskeleton in smooth muscle and cialized nonmuscle type of cell, not a smooth muscle nonmuscle cells, respectively, and 3) laminin and 4) cell. -
Reaction to Injury & Regeneration
Reaction to Injury & Regeneration Steven McLoon Department of Neuroscience University of Minnesota 1 The adult mammalian central nervous system has the lowest regenerative capacity of all organ systems. 2 3 Reaction to Axotomy Function distal to the axon cut is lost. (immediate) 4 Reaction to Axotomy • Spinal cord injury results in an immediate loss of sensation and muscle paralysis below the level of the injury. Spinal cord injury can be partial or complete, and the sensory/motor loss depends on which axons are injured. • Peripheral nerve injury results in an immediate loss of sensation and muscle paralysis in the areas served by the injured nerve distal to the site of injury. 5 Reaction to Axotomy K+ leaks out of the cell and Na+/Ca++ leak into the cell. (seconds) Proximal and distal segments of the axon reseal slightly away from the cut ends. (~2 hrs) Subsequent anterograde & retrograde effects … 6 Anterograde Effects (Wallerian Degeneration) Axon swells. (within 12 hrs) Axolema and mitochondria begin to fragment. (within 3 days) Myelin not associated with a viable axon begins to fragment. (within 1 wk) Astrocytes or Schwann cells proliferate (within 1 wk), which can continue for over a month. Results in >10x the original number of cells. Microglia (or macrophages in the PNS) invade the area. Glia and microglia phagocytize debris. (1 month in PNS; >3 months in CNS) 7 Anterograde Effects (Wallerian Degeneration) Degradation of the axon involves self proteolysis: In the ‘Wallerian degeneration slow’ (Wlds) mouse mutation, the distal portion of severed axons are slow to degenerate; the dominant mutation involves a ubiquitin regulatory enzyme. -
Cranial Nerves 1, 5, 7-12
Cranial Nerve I Olfactory Nerve Nerve fiber modality: Special sensory afferent Cranial Nerves 1, 5, 7-12 Function: Olfaction Remarkable features: – Peripheral processes act as sensory receptors (the other special sensory nerves have separate Warren L Felton III, MD receptors) Professor and Associate Chair of Clinical – Primary afferent neurons undergo continuous Activities, Department of Neurology replacement throughout life Associate Professor of Ophthalmology – Primary afferent neurons synapse with secondary neurons in the olfactory bulb without synapsing Chair, Division of Neuro-Ophthalmology first in the thalamus (as do all other sensory VCU School of Medicine neurons) – Pathways to cortical areas are entirely ipsilateral 1 2 Crania Nerve I Cranial Nerve I Clinical Testing Pathology Anosmia, hyposmia: loss of or impaired Frequently overlooked in neurologic olfaction examination – 1% of population, 50% of population >60 years Aromatic stimulus placed under each – Note: patients with bilateral anosmia often report nostril with the other nostril occluded, eg impaired taste (ageusia, hypogeusia), though coffee, cloves, or soap taste is normal when tested Note that noxious stimuli such as Dysosmia: disordered olfaction ammonia are not used due to concomitant – Parosmia: distorted olfaction stimulation of CN V – Olfactory hallucination: presence of perceived odor in the absence of odor Quantitative clinical tests are available: • Aura preceding complex partial seizures of eg, University of Pennsylvania Smell temporal lobe origin -
Lancl1 Promotes Motor Neuron Survival and Extends the Lifespan of Amyotrophic Lateral Sclerosis Mice
Cell Death & Differentiation (2020) 27:1369–1382 https://doi.org/10.1038/s41418-019-0422-6 ARTICLE LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice 1 1 1 1 1 1 1 Honglin Tan ● Mina Chen ● Dejiang Pang ● Xiaoqiang Xia ● Chongyangzi Du ● Wanchun Yang ● Yiyuan Cui ● 1,2 1 1,3 4 4 3 1,5 Chao Huang ● Wanxiang Jiang ● Dandan Bi ● Chunyu Li ● Huifang Shang ● Paul F. Worley ● Bo Xiao Received: 19 November 2018 / Revised: 3 September 2019 / Accepted: 6 September 2019 / Published online: 30 September 2019 © The Author(s) 2019. This article is published with open access Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Improving neuronal survival in ALS remains a significant challenge. Previously, we identified Lanthionine synthetase C-like protein 1 (LanCL1) as a neuronal antioxidant defense gene, the genetic deletion of which causes apoptotic neurodegeneration in the brain. Here, we report in vivo data using the transgenic SOD1G93A mouse model of ALS indicating that CNS-specific expression of LanCL1 transgene extends lifespan, delays disease onset, decelerates symptomatic progression, and improves motor performance of SOD1G93A mice. Conversely, CNS-specific deletion of fl 1234567890();,: 1234567890();,: LanCL1 leads to neurodegenerative phenotypes, including motor neuron loss, neuroin ammation, and oxidative damage. Analysis reveals that LanCL1 is a positive regulator of AKT activity, and LanCL1 overexpression restores the impaired AKT activity in ALS model mice. These findings indicate that LanCL1 regulates neuronal survival through an alternative mechanism, and suggest a new therapeutic target in ALS. -
The Myelin-Forming Cells of the Nervous System (Oligodendrocytes and Schwann Cells)
The Myelin-Forming Cells of the Nervous System (oligodendrocytes and Schwann cells) Oligodendrocyte Schwann Cell Oligodendrocyte function Saltatory (jumping) nerve conduction Oligodendroglia PMD PMD Saltatory (jumping) nerve conduction Investigating the Myelinogenic Potential of Individual Oligodendrocytes In Vivo Sparse Labeling of Oligodendrocytes CNPase-GFP Variegated expression under the MBP-enhancer Cerebral Cortex Corpus Callosum Cerebral Cortex Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Ant Commissure Corpus Callosum Cerebral Cortex Caudate Putamen Piriform Cortex Corpus Callosum Ant Commissure Characterization of Oligodendrocyte Morphology Cerebral Cortex Corpus Callosum Caudate Putamen Cerebellum Brain Stem Spinal Cord Oligodendrocytes in disease: Cerebral Palsy ! CP major cause of chronic neurological morbidity and mortality in children ! CP incidence now about 3/1000 live births compared to 1/1000 in 1980 when we started intervening for ELBW ! Of all ELBW {gestation 6 mo, Wt. 0.5kg} , 10-15% develop CP ! Prematurely born children prone to white matter injury {WMI}, principle reason for the increase in incidence of CP ! ! 12 Cerebral Palsy Spectrum of white matter injury ! ! Macro Cystic Micro Cystic Gliotic Khwaja and Volpe 2009 13 Rationale for Repair/Remyelination in Multiple Sclerosis Oligodendrocyte specification oligodendrocytes specified from the pMN after MNs - a ventral source of oligodendrocytes