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C-Boutons and Their Influence on Amyotrophic Lateral Sclerosis Disease Progression.

Authors :
Wells, Tyler L.
Myles, Jacob R.
Akay, Turgay
Source :
Journal of Neuroscience. 9/22/2021, Vol. 41 Issue 38, p8088-8101. 14p.
Publication Year :
2021

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive motor neuron death, where patients usually die within 5 years of diagnosis. Previously, we showed that the C-boutons, which are large cholinergic synapses to motor neurons that modulate motor neuron activity, are necessary for behavioral compensation in mSOD1G93A mice, a mouse model for ALS. We reasoned that, since the C-boutons likely increase the excitability of surviving motor neurons to compensate for motor neuron loss during ALS disease progression, then amplitude modulation through the C-boutons likely increases motor neuron stress and worsens disease progression. By comparing male and female mSOD1G93A mice to mSOD1G93A mice with genetically silenced C-boutons [mSOD1G93A; Dbx1::cre; ChATfl/fl (mSOD1G93A/Coff)], we show that the Cboutons do not influence the humane end point of mSOD1G93A mice; however, our histologic analysis shows that C-bouton silencing significantly improves fast-twitch muscle innervation over time. Using immunohistology, we also show that the Cboutons are active in a task-dependent manner, and that symptomatic mSOD1G93A mice show significantly higher C-bouton activity than wild-type mice during low-intensity walking. Last, by using behavioral analysis, we provide evidence that C-bouton silencing in combination with swimming is beneficial for the behavioral capabilities of mSOD1G93A mice. Our observations suggest that manipulating the C-boutons in combination with a modulatory-targeted training program may therefore be beneficial for ALS patients and could result in improved mobility and quality of life. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02706474
Volume :
41
Issue :
38
Database :
Academic Search Index
Journal :
Journal of Neuroscience
Publication Type :
Academic Journal
Accession number :
152665960
Full Text :
https://doi.org/10.1523/JNEUROSCI.0660-21.2021