Arc expression and protein-protein interactions in a mouse model of Alzheimer’s disease. Exercise- and novelty-induced changes in Arc, BDNF, and PS1 expression and Arc PS1 interaction in APP/PS1 and WT mice

Abstract

The overarching goal of this project was to help elucidate how some of the molecular mechanisms behind memory and learning differ between healthy brains and those with neurodegenerative diseases, specifically by studying changes involving the immediate early gene Arc, believed to be an essential regulator of synaptic plasticity. Expression of Arc protein, BDNF, and PS1 in the frontal cortex of APP/PS1 and WT mice housed in standard or enriched environments was compared using Western blotting. The results indicated that Arc expression did not differ significantly between the groups, BDNF expression was higher in mice housed in enriched environments, and PS1 expression was higher in the APP/PS1 mice, likely as a result of expressing a mutant PS1 protein in addition to the endogenous. Further, the project was concentrated on optimization of a co-immunoprecipitation protocol with the objective to study differences in the interaction between Arc and PS1 in APP/PS1 and WT mice. Application of the protocol to frontal cortex tissue from the two strains of mice housed in standard or enriched environments indicated no statistically significant difference in amount of immunoprecipitated Arc and PS1 among the groups of mice, moreover, results suggested that robust co-immunoprecipitation of PS1 with Arc or vice versa requires a continued optimization process.