Neuromuscular junction pathology is correlated with differential motor unit vulnerability in spinal and bulbar muscular atrophy.
Motor neuron
Neuromuscular junction
SBMA
Skeletal muscle
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
05 07 2022
05 07 2022
Historique:
received:
13
05
2022
accepted:
23
06
2022
entrez:
5
7
2022
pubmed:
6
7
2022
medline:
8
7
2022
Statut:
epublish
Résumé
Spinal and bulbar muscular atrophy (SBMA) is an X-linked, neuromuscular neurodegenerative disease for which there is no cure. The disease is characterized by a selective decrease in fast-muscle power (e.g., tongue pressure, grip strength) accompanied by a selective loss of fast-twitch muscle fibers. However, the relationship between neuromuscular junction (NMJ) pathology and fast-twitch motor unit vulnerability has yet to be explored. In this study, we used a cross-model comparison of two mouse models of SBMA to evaluate neuromuscular junction pathology, glycolytic-to-oxidative fiber-type switching, and cytoskeletal alterations in pre- and postsynaptic termini of tibialis anterior (TA), gastrocnemius, and soleus hindlimb muscles. We observed significantly increased NMJ and myofiber pathology in fast-twitch, glycolytic motor units of the TA and gastrocnemius compared to slow-twitch, oxidative motor units of the soleus, as seen by decreased pre- and post-synaptic membrane area, decreased pre- and post-synaptic membrane colocalization, increased acetylcholine receptor compactness, a decrease in endplate area and complexity, and deficits in neurofilament heavy chain. Our data also show evidence for metabolic dysregulation and myofiber atrophy that correlate with severity of NMJ pathology. We propose a model in which the dynamic communicative relationship between the motor neuron and muscle, along with the developmental subtype of the muscle, promotes motor unit subtype specific vulnerability, metabolic alterations, and NMJ pathology.
Identifiants
pubmed: 35791011
doi: 10.1186/s40478-022-01402-y
pii: 10.1186/s40478-022-01402-y
pmc: PMC9258097
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
97Subventions
Organisme : NINDS NIH HHS
ID : R01 NS119873
Pays : United States
Organisme : NINDS NIH HHS
ID : R01NS090335
Pays : United States
Organisme : NINDS NIH HHS
ID : R01NS119873
Pays : United States
Informations de copyright
© 2022. The Author(s).
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