Exercise affects energy metabolism and neural plasticity‐related proteins in the hippocampus as revealed by proteomic analysis

Abstract Studies were conducted to evaluate the effect of a brief voluntary exercise period on the expression pattern and post‐translational modification of multiple protein classes in the rat hippocampus using proteomics. An analysis of 80 protein spots of relative high abundance on two‐dimensional gels revealed that approximately 90% of the proteins identified were associated with energy metabolism and synaptic plasticity. Exercise up‐regulated proteins involved in four aspects of energy metabolism, i.e. glycolysis, ATP synthesis, ATP transduction and glutamate turnover. Specifically, we found increases in fructose‐bisphosphate aldolase C, phosphoglycerate kinase 1, mitochondrial ATP synthase, ubiquitous mitochondrial creatine kinase and glutamate dehydrogenase 1. Exercise also up‐regulated specific synaptic‐plasticity‐related proteins, the cytoskeletal protein α‐internexin and molecular chaperones (chaperonin‐containing TCP‐1, neuronal protein 22, heat shock 60‐kDa protein 1 and heat shock protein 8). Western blot was used to confirm the direction and magnitude of change in ubiquitous mitochondrial creatine kinase, an enzyme essential for transducing mitochondrial‐derived ATP to sites of high‐energy demand such as the synapse. Protein phosphorylation visualized by Pro‐Q Diamond fluorescent staining showed that neurofilament light polypeptide, glial fibrillary acidic protein, heat shock protein 8 and transcriptional activator protein pur‐alpha were more intensely phosphorylated with exercise as compared with sedentary control levels. Our results, together with the fact that most of the proteins that we found to be up‐regulated have been implicated in cognitive function, support a mechanism by which exercise uses processes of energy metabolism and synaptic plasticity to promote brain health.