Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo.
Dis Model Mech
; 16(10)2023 10 01.
Article
in En
| MEDLINE
| ID: mdl-37756598
ABSTRACT
Motor neuron (MN) loss is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS). Histone deacetylase 4 (HDAC4) is one of several factors involved in nerve-muscle communication during MN loss, hindering muscle reinnervation, as shown in humans and in animal models of ALS, and may explain the differential progression observed in patients with ALS - rapid versus slow progression. In this work, we inhibited HDAC4 activity through the administration of a pan-histone deacetylase inhibitor, sodium butyrate, in an in vivo model of chronic spinal MN death induced by AMPA-mediated excitotoxicity. We infused AMPA into the spinal cord at low and high doses, which mimic the rapid and slow progression observed in humans, respectively. We found that muscle HDAC4 expression was increased by high-dose infusion of AMPA. Treatment of animals with sodium butyrate further decreased expression of muscle HDAC4, although non-significantly, and did not prevent the paralysis or the MN loss induced by AMPA infusion. These results inform on the role of muscle HDAC4 in MN degeneration in vivo and provide insights for the search for more suitable therapeutic strategies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyotrophic Lateral Sclerosis
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Dis Model Mech
Journal subject:
MEDICINA
Year:
2023
Document type:
Article
Affiliation country: