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 alpha-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.

Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation

“…These changes were indicative of restoration of the cytoskeletal structure, showing how exercise combated the development of structural defects induced by MS that may be detrimental to normal neuron functioning. Reports of voluntary exercise improving dendritic structure (Redila & Christie, 2006) and increasing β-tubulin in the adult rat hippocampus (Ding et al 2006) support this interpretation.…”

Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

“…Voluntary running is known to increase cell proliferation and neurogenesis in the hippocampus of rodents (20)(21)(22), with concomitant improvements in cognitive function, spatial memory, and learning (23)(24)(25). Exercise also significantly alters the microenvironment of the hippocampus in rodents, with increased growth factor expression (26,27) and synaptic plasticity (28,29). In humans, exercise is known to improve cognitive function (30,31) and to reduce the onset and progression of dementia, as recently reviewed (32).…”

Proteomics of the Synapse – A Quantitative Approach to Neuronal Plasticity

“…Likewise synaptic activation as such does not necessarily lead to an engram that can be easily detected at the protein level. Even an enriched environment or simple physical exercise can lead to the expression of several plasticity-related genes in the hippocampus and dramatic changes in the synaptic proteome that can obscure the findings (144,145). In other terms the number of control experiments to elucidate a learning-induced change in a small number of synapses is high and usually outside of the scope of a single study.…”