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 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.

scholarly journals BPAG1n4 is essential for retrograde axonal transport in sensory neurons

2003 ◽  
Vol 163 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Jia-Jia Liu ◽  
Jianqing Ding ◽  
Anthony S. Kowal ◽  
Timothy Nardine ◽  
Elizabeth Allen ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Sensory Neurons ◽  
Axonal Degeneration ◽  
Retrograde Axonal Transport ◽  
Binding Assays ◽  
Yeast Two Hybrid ◽  
Cytoskeletal Networks ◽  
Two Hybrid ◽  
Hybrid Screening

Disruption of the BPAG1 (bullous pemphigoid antigen 1) gene results in progressive deterioration in motor function and devastating sensory neurodegeneration in the null mice. We have previously demonstrated that BPAG1n1 and BPAG1n3 play important roles in organizing cytoskeletal networks in vivo. Here, we characterize functions of a novel BPAG1 neuronal isoform, BPAG1n4. Results obtained from yeast two-hybrid screening, blot overlay binding assays, and coimmunoprecipitations demonstrate that BPAG1n4 interacts directly with dynactin p150Glued through its unique ezrin/radixin/moesin domain. Studies using double immunofluorescent microscopy and ultrastructural analysis reveal physiological colocalization of BPAG1n4 with dynactin/dynein. Disruption of the interaction between BPAG1n4 and dynactin results in severe defects in retrograde axonal transport. We conclude that BPAG1n4 plays an essential role in retrograde axonal transport in sensory neurons. These findings might advance our understanding of pathogenesis of axonal degeneration and neuronal death.

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
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