Adult hippocampal neurogenesis and c-Fos induction during escalation of voluntary wheel running in C57BL/6J mice

Abstract

Voluntary wheel running activates dentate gyrus granule neurons and increases adult hippocampal neurogenesis. Average daily running distance typically increases over a period of 3 weeks in rodents. Whether neurogenesis and cell activation are greater at the peak of running as compared to the initial escalation period is not known. Therefore, adult C57BL/6J male mice received 5 days of BrdU injections, at the same age, to label dividing cells during the onset of wheel access or after 21 days during peak levels of running or in sedentary conditions. Mice were sampled either 24 hours or 25 days after the last BrdU injection to measure cell proliferation and survival, respectively. Immunohistochemistry was performed on brain sections to identify the numbers of proliferating BrdU labeled cells, and new neurons (BrdU/NeuN co-labeled) in the dentate gyrus. Ki67 was used as an additional mitotic marker. The induction of c-Fos was used to identify neurons activated from running. Mice ran approximately half as far during the first 5 days as compared to after 21 days. Running increased Ki67 cells at the onset but after 21 days levels were similar to sedentary. Numbers of BrdU cells were similar in all groups 24 hours after the final injection. However, after 25 days, running approximately doubled the survival of new neurons born either at the onset or peak of running. These changes co-varied with c-Fos expression. We conclude that sustained running maintains a stable rate of neurogenesis above sedentary via activity-dependent increases in differentiation and survival, not proliferation, of progenitor cells in the C57BL/6J model.

Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

“…Though previous studies have reported a stimulating effect of running on proliferation under comparable conditions [34], our data are in line with a recent study reporting that proliferation is only increased at the onset of wheel running and returns to baseline levels after 21 days of running [35].…”

Mesolimbic transcriptional response to hedonic substitution of voluntary exercise and voluntary ethanol consumption

“…In one of the few studies examining the influence of exercise on ethanol behaviors, Leasure and Nixon (2009) demonstrated exercise’s ability to protect hippocampal cells from the effects of binge ethanol consumption [49]. These findings complement other work showing the ability of exercise to initiate neurogenesis in the hippocampus [50,51], as well as other studies showing that changes in Bdnf expression result in changes in ethanol behaviors [reviews 39,52]. Alterations in the hippocampus due to exercise may influence the signaling between the striatum and hippocampus, affecting the reward response to ethanol drinking.…”

Exercise but not (–)-epigallocatechin-3-gallate or β-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice

“…We hypothesize that these nutritional compounds regardless of their dose or duration will have weak influence on adult hippocampal neurogenesis. Our hypothesis is based on the negative results we obtained in the current study and the idea that levels of adult hippocampal neurogenesis are heavily influenced by levels of physical activity [8,23,31], and subsequent activation of the dentate gyrus of the hippocampus [29,30,62], something we think is unlikely to happen with mere addition of single micronutrients into the diet.…”