![]() ![]() This BDNF-mediated enhancement of transport was also observed in primary ventral horn neuronal cultures. We report that despite displaying similar basal transport speeds, stimulation of wild-type MNs with BDNF enhances in vivo trafficking of signalling endosomes specifically in FMNs. The main aim of this investigation was to determine the effects of brain-derived neurotrophic factor (BDNF) on in vivo axonal transport in different α-motor neuron (MN) subtypes in wild-type (WT) and SOD1 G93A mice. Strikingly, in ALS, fast motor neurons (FMNs) degenerate first whereas slow motor neurons (SMNs) are more resistant, and this is a currently unexplained phenomenon. Deficits in axonal transport have been detected at pre-symptomatic stages in the SOD1 G93A and TDP-43 M337V mouse models of amyotrophic lateral sclerosis (ALS), suggesting that impairments in this critical process are fundamental for disease pathogenesis. Secondary antibodies used in this study.Īxonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, and is needed for neuronal development, function, and survival. Primary antibodies used in this study Table S4. Number of animals, axons, cargoes and frame-to-frame movements assessed for each primary ventral horn culture used for in vitro axonal transport experiments Table S3. Number of animals, axons, cargoes and frame-to-frame movements assessed for each in vivo axonal transport experimental group Table S2. TrkB and p75 NTR expression at the neuromuscular junction (NMJ) in WT and SOD1G93A tibialis anterior and soleus muscles Table S1. Fast motor axon diameters decrease with progression of SOD1 G93A pathology Figure S6. Retrograde transport dynamics of signalling endosomes in axons innervating lateral gastrocnemius (LG) and soleus muscles in WT and SOD1 G93A mice Figure S5. Kymographs of in vivo retrograde transport of HCT-555-positive signalling endosomes from live, anesthetised mice Figure S4. TrkB.FL, truncated TrkB and p75 NTR levels do not differ between wild-type (WT) and SOD1 G93A primary embryonic ventral horn neurons in mass culture Figure S3. Retrograde transport dynamics of signalling endosomes in wild-type mice Figure S2. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Īdditional file 2. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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