Distinct behavioral effects of short-term voluntary running in phosphatase and tensin homolog deleted on chromosome 10 neuronal haploinsufficient mice

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a tumor suppressor with functions related to its phosphatase activity. PTEN plays various roles, such as cell proliferation, survival, and migration and is involved in neurogenesis and synaptic plasticity in the central nervous system. It has been reported that running could have protective effects against the aging process and neurodegenerative diseases. Therefore, we aimed to evaluate the effects of physical exercise on behavioral and biochemical aspects of PTEN-conditioned knockout female mice. We observed that 10 days of voluntary running positively affected fear memory but caused no changes in anxiety-like behavior. However, it was unable to counteract the social recognition memory deficit in PTEN neuronal haploinsufficient mice. In terms of biochemical aspects, we observed that short-term running reduced S6 phosphorylation in PTEN heterozygous mice and PTEN protein expression independent of the genotype. In addition, PTEN heterozygous mice presented reduced N-methyl-D-aspartate subunit NR1 protein expression. Our results regarding decreased S6 phosphorylation in HT mice suggest that short-term voluntary running could have induced a protective effect in reducing dysregulated cell growth, possibly related to the downregulation of tumor suppressor expression/activity such as PTEN. Moreover, running induced distinct behavioral effects in PTEN-conditioned knockout mice.