It is widely accepted that genes interact with environment to affect brain function and behavior. Exercise is a potent environmental factor with known benefits for physical health such as strength and stamina. The recent discovery that exercise can also enhance cognitive performance has generated much enthusiasm and interest, but mechanisms are far less understood. A growing body of evidence in rodent animal models suggests that exercise is a natural generator of neural plasticity. One example is growth of new neurons in the hippocampus, which is strongly regulated by exercise along with many other changes (e.g., trophic factors, growth factors, capillaries). Harnessing mechanisms of the natural generator could be useful for treating a wide range of neurological problems such as cognitive aging, neurodegenerative disease, stroke, or head trauma. One approach to find a mechanism is to systematically block changes in each hypothesized substrate (e.g., new neurons). Another is unbiased exploration of genetic mechanisms. We propose both. Preliminary data suggest that exercise induced changes in hippocampal neurogenesis and learning vary depending on genotype in mice.
Aims 1 and 2 are to identify sets of genotypes that display larger versus smaller benefits. This crucial information will be contributed to a database of phenotypic and genetic information on these strains, and used in the future to identify mechanisms for cognitive benefits of exercise at multiple levels of biological organization from genes to physiology to behavior. In addition to laying the groundwork for the genetic analysis, we also propose an innovative method in aim 3 to reduce neurogenesis in exercising mice, focal gamma radiation, to directly test the hypothesis that new neurons are required for enhanced learning from exercise in predisposed genotypes. For this, we propose to use the genotype C57BL/6J, as proof of principal, because a strong correlation between exercise, neurogenesis, and learning is well established for this strain.
The goal of this project is to discover mechanisms for pro cognitive effects of exercise at multiple levels of biological organization from genes to physiology to behavior.
|Hamilton, G F; Hernandez, I J; Krebs, C P et al. (2017) Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise. Neuroscience 352:52-63|
|Hamilton, G F; Bucko, P J; Miller, D S et al. (2016) Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise. Behav Brain Res 314:96-105|
|Majdak, Petra; Grogan, Elizabeth L; Gogola, Joseph V et al. (2016) The impact of maternal neglect on genetic hyperactivity. Behav Brain Res 313:282-92|
|Rendeiro, Catarina; Masnik, Ashley M; Mun, Jonathan G et al. (2015) Fructose decreases physical activity and increases body fat without affecting hippocampal neurogenesis and learning relative to an isocaloric glucose diet. Sci Rep 5:9589|
|Hamilton, G F; Majdak, P; Miller, D S et al. (2015) Evaluation of a C57BL/6J × 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis. Brain Plast 1:83-95|
|Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R et al. (2015) Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration. J Neurochem 135:1038-48|
|Bhattacharya, Tushar K; Pence, Brandt D; Ossyra, Jessica M et al. (2015) Exercise but not (-)-epigallocatechin-3-gallate or ?-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice. Physiol Behav 145:29-37|
|Merritt, Jennifer R; Rhodes, Justin S (2015) Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze. Behav Brain Res 280:62-71|
|Rendeiro, Catarina; Rhodes, Justin S; Spencer, Jeremy P E (2015) The mechanisms of action of flavonoids in the brain: Direct versus indirect effects. Neurochem Int 89:126-39|
|Majdak, Petra; Bucko, Paula J; Holloway, Ashley L et al. (2014) Behavioral and pharmacological evaluation of a selectively bred mouse model of home cage hyperactivity. Behav Genet 44:516-34|
Showing the most recent 10 out of 29 publications