All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis

Abstract

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

Fig. 1

Exercise but not enrichment increases DG neurogenesis. Female C57Bl/6 mice (n = 10 per group) were housed in large cages (30”×33”×8”) as follows: a Control (CON). b Running (RUN). c Enriched environment only (EEO). d Enrichment and running (EER), this cage contained enrichment objects similar to (c), as well as 10 running wheels. e Overview of the experimental cages. (f–g) Confocal images of BrdU-positive cells in the dentate gyrus in sections derived from mice housed in (f) CON, (g) RUN, (h) EEO, or (i) EER conditions. Sections were immunofluorescent double-labeled for BrdU (green) and NeuN (red) indicating neuronal phenotype (Kobilo et al. 2011a)

Fig. 2

Exercise is not beneficial in a mouse model of Huntington's disease (HD) N171-82Q. a Morphology of Doublecortin (DCX) expressing immature neurons in the DG of WT and HD mice. Dendritic branching complexity of DCX-labeled (red) immature neurons was reduced in the transgenic mice, HD sedentary (HTS) and HD runner (HTR) compared to Wildtype sedentary (WTS) and Wildtype runner (WTR). Granular cell layer neurons were labeled with DAPI (blue). b Timeline of experiment in weeks of age for the subset of mice tested for behavior (S) and mice evaluated over their lifespan (L) mice. BrdU was injected over the first 10 days of the study. Behavioral testing was carried out from week 12 to 15 and mice (S) were sacrificed (SAC) at approximately 16 weeks of age. Survival analysis indicated that HD mice died between 11 and 26 weeks of age. c Onset of disease symptoms such as hunched back, poor grooming and involuntary shaking occurred earlier in HD runners; * p<0.03. d Lifespan did not change as a result of exercise. e There was no significant difference between the groups in running distance over the duration of the experiment. (f–g) Exercise may exacerbate locomotor deficits in HD mice. (f) The latency to fall off an accelerating rotarod was shorter in HTR mice than in all other groups; * p<0.03. g The total number of falls from the rotarod over 5 min was increased in HD runners compared to WT mice; * p<0.02, HTR versus WTS and WTR. h The total distance traveled over 30 min in an open field was reduced in HD mice compared to WT mice, specifically in HTR mice compared to WTR mice; * p<0.03. Abbreviations: MWM Morris water maze; OF Open field; S Subset tested for behavior; L Lifespan group; SAC sacrificed (Potter et al. 2010)

Fig. 3

Running but not antidepressants enhances neurogenesis. Photomicrographs of the dentate gyrus in sections derived from mice injected with saline, duloxetine 6 mg/kg, fluoxetine 18 mg/kg, or housed with a running wheel for 28 days. BrdU labeled cells (green) and cells labeled with the neuronal marker NeuN (red). Co-labeling analysis indicated that running mice had more than 2-fold increase in the number of new neurons compared to all the other groups (Marlatt et al. 2010)