Lifelong parental voluntary wheel running increases offspring hippocampal Pgc-1α mRNA expression but not mitochondrial content or Bdnf expression

Abstract

When exercise is initiated during pregnancy, offspring of physically active mothers have higher hippocampal expression of brain-derived neurotrophic factor (Bdnf) and other plasticity-associated and mitochondria-associated genes, resulting in hippocampal structural and functional adaptations. In the present study, we examined the effects of lifelong parental voluntary wheel running (before, during, and after pregnancy) on offspring hippocampal mRNA expression of genes implicated in the exercise-induced improvement of cognitive function. C57BL/6 mice were individually housed at 8 weeks of age with (EX, n=20) or without (SED, n=20) access to a computer-monitored voluntary running wheel for 12 weeks before breeding. EX breeders maintained access to the voluntary running wheel throughout breeding, pregnancy, and lactation. Male offspring were housed in sedentary cages, regardless of the parental group, and were killed at 8 (n=18) or 28 weeks (n=19). PCR was used to assess mRNA expression of several genes and mitochondrial content (ratio of mitochondrial to nuclear DNA) in hippocampal homogenates. We found significantly higher peroxisome proliferator-activated receptor γ coactivator 1 α (Pgc-1α) mRNA expression in EX offspring compared with SED offspring at 8 weeks (P=0.04), although the effect was no longer present at 28 weeks. There was no difference in mitochondrial content or expression of Bdnf or any other mRNA target between offspring at 8 and 28 weeks. In contrast to exercise initiated during pregnancy, parental voluntary physical activity initiated early in life and maintained throughout pregnancy has little effect on offspring mRNA expression of genes implicated in exercise-induced hippocampal plasticity.

Figure 1

Average running activity of mice. Data are shown as average distance run over 24 hours per week. Running data were not collected during mating due to the presence of two mice in the cage and the inability to determine which mouse was using the running wheel. The litters were delivered between 23 and 24 weeks on the timeline. There was a six-day span between first and last litter, thus pre-weaned mice had access to the wheel. We cannot rule out the possibility that pre-weaned mice are contributing to recorded wheel revolutions during week 27.

Figure 2

(A–B). Whole hippocampal homogenate mRNA levels in F₁ 8 week old male offspring of exercise (n=10) and sedentary (n=8) parents. Bars represent mean (±SEM) mRNA expression relative to Gapdh mRNA expression. * denotes significance at p<0.05.

Figure 3

Mitochondrial DNA content in F₁ 8 wk and 28wk old male offspring of exercise and sedentary parents. There were no significant differences in CytB mitochondrial DNA content relative to ActB DNA content between offspring of exercise and sedentary parents at 8 weeks or 28 weeks of age. Results are means ±SEM.

Figure 4

(A–B). Whole hippocampal homogenate mRNA levels in F₁ 28 week old male offspring of exercise (n=9) and sedentary (n=10) parents. Bars represent mean (±SEM) mRNA expression relative to Gapdh mRNA expression. * denotes significance at p<0.05.