Tosolini, Andrew P;
Sleigh, James N;
Surana, Sunaina;
Rhymes, Elena R;
Cahalan, Stephen D;
Schiavo, Giampietro;
(2021)
BDNF-regulation of in vivo axonal transport is selectively impaired in fast motor neurons in SOD1ᴳ⁹³ᴬ mice.
Presented at: EMBO Workshop: Axons 2021: Structure and function, Virtual conference.
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Abstract
Background: Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments of neurons, and is needed for neuronal development, function and survival. ALS mice, including SOD1G93A and TDP- 43M337V mice, display in vivo deficits in axonal transport pre-symptomatically suggesting that impairment contributes to disease. The aim of this study is to determine the influence of brain-derived neurotrophic factor (BDNF) and α-motor neuron (MN) subtypes on axonal transport. / Methods: Signalling endosome axonal transport was visualised in vivo with intramuscular injections of a fluorescently-labelled atoxic fragment of tetanus neurotoxin (HcT). HcT was delivered into the tibialis anterior (TA) or soleus muscles of wild-type (WT) and SOD1G93A mice +/- 25ng of recombinant BDNF. 4+ hours later, sciatic nerves were exposed in live, anaesthetised animals, and imaged using time-lapse confocal-microscopy at 37°C. Retrogradely transported signalling endosomes within single axons were tracked using the TrackMate plugin (FIJI/ImageJ). BDNF, TrkB and p75NTR levels were assessed in muscles, neuromuscular junctions and sciatic nerves in WT/SOD1G93A mice. / Results: Basal axonal transport analysis reveals that signalling endosome dynamics are similar between MN/muscle subgroups. BDNF-stimulation significantly enhanced axonal transport dynamics in WT MNs innervating TA only, and this was significantly impaired in SOD1G93A mice. BDNF, TrkB and p75NTR levels were differentially affected in both muscles and sciatic nerve in SOD1G93A mice. / Discussion and Conclusions: These data indicate that different MN/muscle subgroups have distinct axonal transport features and are differentially afflicted in SOD1G93A mice, and may reveal novel clues about selective MN vulnerability in ALS.
| Type: | Poster |
|---|---|
| Title: | BDNF-regulation of in vivo axonal transport is selectively impaired in fast motor neurons in SOD1ᴳ⁹³ᴬ mice |
| Event: | EMBO Workshop: Axons 2021: Structure and function |
| Location: | Virtual conference |
| Dates: | 04 - 07 October 2021 |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | https://meetings.embo.org/event/20-axons |
| Language: | English |
| 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/10161691 |
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