Détail du document
Identifiant

doi:10.1186/s40478-022-01418-4...

Auteur
Tosolini, Andrew P. Sleigh, James N. Surana, Sunaina Rhymes, Elena R. Cahalan, Stephen D. Schiavo, Giampietro
Langue
en
Editeur

BioMed Central

Catégorie

Neurology

Année

2022

Date de référencement

08/12/2022

Mots clés
axonal transport amyotrophic lateral sclerosis motor neuron bdnf trkb p75 mice fmns vivo als bdnf transport
Métrique

Résumé

Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, and is needed for neuronal development, function, and survival.

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.

Strikingly, in ALS, fast motor neurons (FMNs) degenerate first whereas slow motor neurons (SMNs) are more resistant, and this is a currently unexplained phenomenon.

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.

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.

This BDNF-mediated enhancement of transport was also observed in primary ventral horn neuronal cultures.

However, FMNs display selective impairment of axonal transport in vivo in symptomatic SOD1^G93A mice , and are refractory to BDNF stimulation, a phenotype that was also observed in primary embryonic SOD1^G93A neurons.

Furthermore, symptomatic SOD1^G93A mice display upregulation of the classical non-pro-survival truncated TrkB and p75^NTR receptors in muscles, sciatic nerves, and Schwann cells.

Altogether, these data indicate that cell- and non-cell autonomous BDNF signalling is impaired in SOD1^G93A MNs, thus identifying a new key deficit in ALS.

Tosolini, Andrew P.,Sleigh, James N.,Surana, Sunaina,Rhymes, Elena R.,Cahalan, Stephen D.,Schiavo, Giampietro, 2022, BDNF-dependent modulation of axonal transport is selectively impaired in ALS, BioMed Central

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