PUBLICATION
Trimetazidine stimulates intracellular Ca2+ transients and zebrafish locomotor activity in spinal neurons
- Authors
- Bernardi, S., Vitolo, S., Gabellini, C., Marchese, M., Ferraro, E.
- ID
- ZDB-PUB-250702-16
- Date
- 2025
- Source
- Scientific Reports 15: 2285422854 (Journal)
- Registered Authors
- Keywords
- Aging, Amyotrophic lateral sclerosis, Motor neuron disease, Neuro-muscular junction, Skeletal muscle, Spinal cord, Trimetazidine
- MeSH Terms
-
- Animals
- Trimetazidine*/pharmacology
- Calcium*/metabolism
- Spinal Cord*/cytology
- Spinal Cord*/drug effects
- Spinal Cord*/metabolism
- Zebrafish/physiology
- Locomotion*/drug effects
- Animals, Genetically Modified
- Motor Neurons*/drug effects
- Motor Neurons*/metabolism
- Calcium Signaling*/drug effects
- PubMed
- 40594383 Full text @ Sci. Rep.
Citation
Bernardi, S., Vitolo, S., Gabellini, C., Marchese, M., Ferraro, E. (2025) Trimetazidine stimulates intracellular Ca2+ transients and zebrafish locomotor activity in spinal neurons. Scientific Reports. 15:2285422854.
Abstract
The metabolic modulator trimetazidine (TMZ) is an antianginal recently found to improve skeletal muscle performance in mice models of sarcopenia and of amyotrophic lateral sclerosis (ALS). The mechanism underlying the effect of TMZ on locomotor activity has been proposed to rely on its ability to enhance metabolic efficiency with a consequent improvement of myogenesis and of neuromuscular junction (NMJ) and muscle function. However, although promising and therefore under clinical trials, the mechanism of action of TMZ has not been clearly disclosed; here we hypothesized that it might involve the modulation of neuronal Ca2+ flows. We studied the effect of TMZ on Ca2+ dynamics in vivo, by using the transgenic zebrafish line Tg(neurod1:GCaMP6f) in which the neuronal expression of the Ca2+ indicator GCaMP allows to visualize Ca2+ dynamics in neurons of zebrafish larvae. By this elegant tool, we demonstrated, for the first time, that TMZ promotes an increase of intracellular Ca2+ transients in zebrafish spinal neurons likely enhancing motor neuron firing, which correlates with enhanced motor performance induced by this drug. Even though elevated intracellular Ca2+ levels have often been associated to neurotoxicity, it is unclear if the neuronal excitability features in some neuro-muscular disorders are compensatory or pathological. Therefore, this newly reported effect of TMZ which transiently and selectively enhances spinal neuron firing deserves to be further detailed and taken into account when the possible repurposing of this drug is proposed for the treatment of neuro-muscular disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping