Integrated metabolomics and proteomics analysis in children with cerebral palsy exposed to botulinum toxin-A.

BACKGROUND

We previously examined plasma metabolic changes before and after botulinum toxin-A injections of cerebral palsy (CP) children and showed that the glycine, serine and threonine metabolism may play a key role in neuritogenesis. This study analysed untargeted metabolomics combined with proteomics of plasma to discussed which substances are meaningfully changed, to what extent they affect the effects of action.

METHODS

Blood samples were collected from 91 children with spastic CP at 4 time points: pre-injection (T1), 1 month post-injection (T2), 3 months post-injection (T3) and 6 months post-injection (T4). Differentially changed metabolites and proteins were selected, and co-expression pathways were constructed to explore the key molecular processes.

RESULTS

A total of 674 proteins and 354 metabolites were identified. The differential metabolites were mainly involved in the linoleic acid metabolism, beta-Alanine metabolism, citrate cycle, pyruvate metabolism and glycolysis or gluconeogenesis. Differential proteins were primarily associated with glucose metabolism, lipid metabolism, immune and inflammation responses. Co-expression pathways showed that ECM-receptor interaction, complement and coagulation cascades, glycolysis or gluconeogenesis, pyruvate metabolism, and linoleic acid metabolism were the main pathways.

CONSLUSIONS: Our results indicated the botulinum toxin-A predominantly activated the glucose metabolism, lipid metabolism, and immune and inflammation responses, and energy metabolism changed significantly in this process.

TRIAL REGISTRATION DETAILS: ChiCTR2000033800, Research on the mechanism of botulinum toxin relieving spasticity in children with cerebral palsy. Approval No. 202023041. Registered 13 June 2020, http://www.chictr.org.cn/showproj.html?proj=52267 .

IMPACT STATEMENT: This is the first study that combined dynamic metabolomics and proteomics analysis to investigate the molecular changes in children with spastic cerebral palsy after botulinum toxin-A injections, which might provide a theoretical reference for the further subsequent study for targets to increase the efficacy and prolong the duration of botulinum toxin-A, and would be a valuable resource for the metabolomics and proteomics field in this group.