Villarroel Campos, David;
Rhymes, Elena R;
Tosolini, Andrew P;
Malik, Bilal;
Vagnoni, Alessio;
Schiavo, GIampietro;
Sleigh, James N;
(2025)
Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age.
Neurobiology of Aging
, 153
pp. 1-9.
10.1016/j.neurobiolaging.2025.05.002.
Preview |
Text
Sleigh_1-s2.0-S0197458025000880-main.pdf Download (2MB) | Preview |
Abstract
A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological diseases. A decline in this essential process has also been identified in many aging models, perhaps compounding age-related neurodegeneration. Via intravital imaging, we recently determined that, despite a reduction in overall motility, the run speed and displacement of anterograde mitochondrial transport were unexpectedly enhanced in 19–22 month-old mouse peripheral nerves. Here, to determine how aging impacts a different axonal cargo, we evaluated in vivo trafficking of signalling endosomes in motor axons of mouse sciatic nerves from 3 to 22 months. Contrasting with mitochondria, we did not detect alterations in signalling endosome speed, but found a consistent rise in pausing that manifested after 18 months. We then treated muscles with brain-derived neurotrophic factor (BDNF), which regulates axonal transport of signalling endosomes in motor neurons; however, we observed no change in the processivity defect at 22 months, consistent with downregulation of the BDNF receptor TrkB at the neuromuscular junction. Together, these findings indicate that aging negatively impacts signalling endosome trafficking in motor axons, likely through dampened BDNF signalling at the motor neuron-muscle interface.
| Type: | Article |
|---|---|
| Title: | Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neurobiolaging.2025.05.002 |
| Publisher version: | https://doi.org/10.1016/j.neurobiolaging.2025.05.0... |
| Language: | English |
| Additional information: | © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Aged, Aging, Intravital imaging, Motor neuron, Neurotrophins, Sciatic nerve, Signalling endosomes, Tropomyosin receptor kinase B (TrkB) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10208984 |
Archive Staff Only
 |
View Item |
