scholarly journals Botulinum Neurotoxins A and E Undergo Retrograde Axonal Transport in Primary Motor Neurons

2012 ◽  
Vol 8 (12) ◽  
pp. e1003087 ◽  
Author(s):  
Laura Restani ◽  
Francesco Giribaldi ◽  
Maria Manich ◽  
Kinga Bercsenyi ◽  
Guillermo Menendez ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Motor Neurons ◽  
Retrograde Axonal Transport ◽  
Botulinum Neurotoxins

scholarly journals Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Alison M. Hixon ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Sialic Acid ◽  
Motor Neuron ◽  
Axonal Transport ◽  
Motor Neurons ◽  
The United States ◽  
Retrograde Axonal Transport ◽  
Spinal Motor Neurons ◽  
Acute Flaccid Myelitis ◽  
Spinal Motor ◽  
Enterovirus D68

ABSTRACTEnterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons.IMPORTANCEEnterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

Endocytosis and retrograde axonal traffic in motor neurons.

2005 ◽  
Vol 72 ◽  
pp. 139-150 ◽  
Author(s):  
Katrin Deinhardt ◽  
Giampietro Schiavo
Keyword(s):  
Spinal Cord ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Molecular Basis ◽  
Retrograde Transport ◽  
Membrane Dynamics ◽  
Transport Pathway ◽  
Precise Control ◽  
Recent Developments ◽  
Botulinum Neurotoxins

Spinal cord motor neurons control voluntary movement by relaying messages that arrive from upper brain centres to the innervated muscles. Despite the importance of motor neurons in human health and disease, the precise control of their membrane dynamics and its effect on motor neuron homoeostasis and survival are poorly understood. In particular, the molecular basis of the co-ordination of specific endocytic events with the axonal retrograde transport pathway is largely unknown. To study these important vesicular trafficking events, we pioneered the use of atoxic fragments of tetanus and botulinum neurotoxins to follow endocytosis and retrograde axonal transport in motor neurons. These neurotoxins bind specifically to pre-synaptic nerve terminals, where they are internalized. Whereas botulinum neurotoxins remain at the neuromuscular junction, tetanus toxin is retrogradely transported along the axon to the cell body, where it is released into the intersynaptic space and is internalized by adjacent inhibitory interneurons. The high neurospecificity and the differential intracellular sorting make tetanus and botulinum neurotoxins ideal tools to study neuronal physiology. In the present review, we discuss recent developments in our understanding of the internalization and trafficking of these molecules in spinal cord motor neurons. Furthermore, we describe the development of a reliable transfection method for motor neurons based on microinjection, which will be extremely useful for dissecting further the molecular basis of membrane dynamics and axonal transport in these cells.

Neuronal Injury Increases Retrograde Axonal Transport of the Neurotrophins to Spinal Sensory Neurons and Motor Neurons via Multiple Receptor Mechanisms

1998 ◽  
Vol 12 (3) ◽  
pp. 105-118 ◽  
Author(s):  
Rory Curtis ◽  
James R. Tonra ◽  
Jennifer L. Stark ◽  
Krystyna M. Adryan ◽  
John S. Park ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neuronal Injury ◽  
Retrograde Axonal Transport ◽  
Multiple Receptor

scholarly journals IGF 1R regulates retrograde axonal transport of signalling endosomes in motor neurons

EMBO Reports ◽  
2020 ◽  
Vol 21 (3) ◽  
Author(s):  
Alexander D Fellows ◽  
Elena R Rhymes ◽  
Katherine L Gibbs ◽  
Linda Greensmith ◽  
Giampietro Schiavo
Keyword(s):  
Axonal Transport ◽  
Motor Neurons ◽  
Retrograde Axonal Transport
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