Neuroscience letters · 2026
Regulation of mitochondrial biogenesis by the 5-HT1F receptor and its agonist in inferior spinal cords after spinal cord injury.
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Zhang Chao, Ren Liqun, Fan Yanfang
Аннотация
BACKGROUND: Muscle spasticity is among the common secondary complications in patients with spinal cord injury (SCI). On the basis of our previous findings, the present study focuses on mitochondrial biogenesis (MB) to further explore the relationship between the regulation of 5-HT1F receptor (5-HT1FR) activity and muscle spasticity following SCI.
METHODS: A stable spasticity model was established in male Wistar rats, which were randomly assigned to low-, medium-, and high-dose lasmiditan (a 5-HT1FR agonist; designated SLL, SLM, and SLH, respectively) and control groups. Spasticity scores were assessed over time in all groups. The expression levels of proteins associated with the PGC-1α signalling pathway were measured, and mitochondrial ultrastructural morphology was examined and compared among the groups.
RESULTS: SCI significantly increased spasticity scores, which peaked on Day 60. Compared with the SCI group, the SLH group exhibited significantly lower spasticity scores on Days 67 and 74 (both P < 0.05), whereas the SLM group showed significant improvement only on Day 74 (P = 0.003). SCI markedly downregulated the mRNA and protein expression of PGC-1α, Nrf1, p-AMPKα, ATP Synβ, and TFAM (all P < 0.05). Lasmiditan restored the expression of these molecules. Notably, the SLH group and SLM group had significantly upregulated ATP Synβ and TFAM expression at both the mRNA and protein levels (P < 0.05). Furthermore, the 5-HT1FR agonist lasmiditan effectively alleviated mitochondrial ultrastructural damage following SCI.
CONCLUSION: Activation of the 5-HT1FR promotes MB in spinal cord tissue below the injury level after SCI. This mechanism may contribute to its therapeutic potential for secondary spasticity.
METHODS: A stable spasticity model was established in male Wistar rats, which were randomly assigned to low-, medium-, and high-dose lasmiditan (a 5-HT1FR agonist; designated SLL, SLM, and SLH, respectively) and control groups. Spasticity scores were assessed over time in all groups. The expression levels of proteins associated with the PGC-1α signalling pathway were measured, and mitochondrial ultrastructural morphology was examined and compared among the groups.
RESULTS: SCI significantly increased spasticity scores, which peaked on Day 60. Compared with the SCI group, the SLH group exhibited significantly lower spasticity scores on Days 67 and 74 (both P < 0.05), whereas the SLM group showed significant improvement only on Day 74 (P = 0.003). SCI markedly downregulated the mRNA and protein expression of PGC-1α, Nrf1, p-AMPKα, ATP Synβ, and TFAM (all P < 0.05). Lasmiditan restored the expression of these molecules. Notably, the SLH group and SLM group had significantly upregulated ATP Synβ and TFAM expression at both the mRNA and protein levels (P < 0.05). Furthermore, the 5-HT1FR agonist lasmiditan effectively alleviated mitochondrial ultrastructural damage following SCI.
CONCLUSION: Activation of the 5-HT1FR promotes MB in spinal cord tissue below the injury level after SCI. This mechanism may contribute to its therapeutic potential for secondary spasticity.