Proteomic changes of the bilateral M1 and spinal cord in hemiplegic cerebral palsy mouse: Effects of constraint-induced movement therapy

Abstract

Hemiplegic cerebral palsy (HCP) is a non-progressive movement and posture disorder that affects one side of the body. Constraint-induced movement therapy (CIMT) can improve the hand function of children with HCP. We used label-free proteomic quantification technology to evaluate proteomic changes in the bilateral M1 and spinal cord in HCP mouse induced by hypoxia/ischemia and CIMT. Nissl staining showed reduced neuron density in the HCP mice’s lesioned and contralesional M1. The rotarod test and grip strength test showed motor dysfunction in mice with HCP and improved motor ability after CIMT. A total of 5147 proteins were identified. Fifty-one, five, and sixty common differentially expressed proteins (DEPs), which were co-regulated by HCP and CIMT, were found in the lesioned M1, the contralesional M1 and the spinal cord respectively. The significant proteins included alpha-centractin, metaxin complex, PKC, septin 11, choline transporter-like proteins, protein 4.1, teneurin-4, and so on, which mainly related to synapse stability, neuronal development and maintenance, axon development, and myelin formation. The KEGG pathways of HCP-induced DEPs mainly related to lipid metabolism, synaptic remodeling, SNARE interactions in vesicular transport and axon formation. The CIMT-induced DEPs were mainly related to synaptic remodeling and axon formation in the lesioned M1 and spinal cord. This study investigated the proteomic changes of the bilateral M1 and spinal cord as well as the CIMT-induced proteomic changes in HCP mice, which might provide new insights into the therapy of HCP.