Muriel Koehl, Francis Chaouloff et al. dans Hippocampus

Running per se stimulates the dendritic arbor of newborn dentate granule cells in mouse hippocampus in a duration-dependent manner. Dostes S, Dubreucq S, Ladevèze E, Marsicano G, Abrous DN, Chaouloff F, Koehl M. Hippocampus. 2015 Nov 25. doi: 10.1002/hipo.22551.

Muriel Koehl et Francis Chaouloff: The original finding from Gage’s laboratory that rodents provided running wheels display increased hippocampal neurogenesis rates in adults is considered a milestone in the research field devoted to the neurobiology of exercise. Thus, besides this observation, different studies have proposed that such a neurogenic impact of exercise might mediate the antidepressant and anxiolytic effects of exercise, as reported in rodents and humans. However, more recent findings, including those from a local team (Dubreucq et al., 2011; 2015 from Marsicano’s team), have questioned the methodology used in the latter publications as the controls to which the runners are compared are usually housed under standard conditions, i.e. without wheels. Indeed, the presence of wheels, although these are locked, was found to bear a significant inhibitory impact on anxiety, in keeping with the well documented anxiolytic impact of environmental enrichments.

Above: illustration of the four experimental conditions created in the experiment. Bottom panel left: Photomicrograph of newborn neurons in the dentate gyrus of one representative mouse for each condition. Bottom panel middle: Representative traces of the dendritic tree of newborn neurons in mice housed in the different conditions. Bottom panel right: Dendritic complexity measured by Sholl analysis.

Furthermore, although running was found to increase the number of newborn neurons, whether it also impacted their dendritic architecture, and thus their network integration, remained unknown. In the present study, we questioned (i) the impact of the housing condition (standard home cage, home cage with a locked wheel, or home cage with a free wheel) on hippocampal neurogenesis and on the architecture of the neurons born during this neurogenesis process, and (ii) how the duration of running (3 h or 24 h/day) impacted these variables.
The results indicate that while the mere presence of a blocked wheel increases cell proliferation, these newborn cells do not survive the initial selection step. On the other hand, running increases in a time-dependent manner both the number and the survival rate of proliferating cells, hence leading to a net increase in the number of newborn neurons. Interestingly, compared to the standard housing condition, the three other housing conditions increase to a large extent the complexity of the dendritic tree of the newborn cells. Moreover, running per se did so again in a time-dependent manner with unlimited access to the running wheels increasing by 500% the total dendritic length.

Altogether, this study highlights first that enrichment linked to a wheel presence can be a confounding factor when analyzing the impact of running, but also and more importantly, that even running sessions of moderate duration significantly impact brain architecture, thus bearing a significant translational relevance to human practice as well as an interesting therapeutic potential.