Research

Exercise is well known to be a powerful modulator of learning and memory. An unmet need in the field of exercise neurobiology is how we can translate our current understanding of exercise mechanisms to therapeutic interventions for maximizing cognitive outcomes in pediatric patients. Research in the Ivy Lab interrogates molecular mechanisms engaged by exercise that are critical to modulating brain function, to determine how they may interact with critical periods of brain development and plasticity. To this end, our lab uses transgenic and biological mouse models to study how early-life exercise can influence neuronal function and behaviors throughout the lifespan. Using a number of molecular biology approaches, and focusing on gene expression and epigenetic modifications, we interrogate the structural and functional development of neuronal circuits after early-life exercise. We have designed a unique mouse model of early-life exercise that allows juvenile and adolescent mice to engage in voluntary wheel running in their home cage. This model was specifically designed for investigating how an early-life experience such as exercise influences the developing brain during postnatal periods of synapse refinement and network establishment. We are using this exercise model to broadly address three key areas of research:

1- Coupling transcriptome and epigenome sequencing to uncover molecular signatures of early-life exercise in the brain.

2- “Rewriting” the effects of early-life adversity with exercise interventions: resilience found in the epigenome.

3- Metabolic adaptations to early-life exercise: identifying biomarkers to ultimately prescribe an exercise “dose” for optimal cognitive outcomes.

IMPACT AND RELEVANCE

We take a basic science research approach to identify novel mechanisms engaged by early-life exercise that can be targeted to have enduring effects on brain function. If this work is translatable to humans, our findings have the potential to inform therapeutic strategies for cognitive dysfunction in children with neurological disorders, emotional disorders, or those that are physically unable to exercise.

Techniques currently used in our lab: Mouse behavioral assays of learning and memory, generation of transgenic mice, real-time quantitative PCR, Chromatin Immunoprecipitation (ChIP), immunohistochemistry and immunofluorescence, gel electrophoresis, golgi impregnation for neuronal and synaptic structure, fluorescence-activated cell sorting (FACS), RNA and ChIP-sequencing.