Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice - PubMed (original) (raw)

Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

Klaus Fabel et al. Front Neurosci. 2009.

Abstract

Voluntary physical exercise (wheel running, RUN) and environmental enrichment both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival-promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR) would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis. Surprisingly, this result indicates that although overall the amount of proliferating cells in the dentate gyrus is poorly predictive of net adult neurogenesis, an increased neurogenic potential nevertheless provides the basis for a greater efficiency of the same survival-promoting stimulus. We thus propose that physical activity can "prime" the neurogenic region of the dentate gyrus for increased neurogenesis in the case the animal is exposed to an additional cognitive stimulus, here represented by the enrichment paradigm.

Keywords: hippocampus; learning; reserve; stem cell.

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Figures

Figure 1

Figure 1

Experimental design. During phase 1 of the experiment mice were either given access to a RUN ad libitum (RUNSTD and RUNENR group) or were housed under standard laboratory conditions (STDSTD and STDENR group). Dividing hippocampal precursor cells were labeled with BrdU during the last 3 days of phase 1. Subsequently, in phase 2 (duration: 35 days), animals were either exposed to an enriched environment (STDENR and RUNENR groups) or housed under standard laboratory conditions (STDSTD and RUNSTD group). Animals were killed after phase 2 was completed and brain tissue was prepared for immunohistochemistry. For further details see Sections “Introduction and Materials and Methods”.

Figure 2

Figure 2

Activity-induced changes in the number of BrdU-labeled cells and new neurons in the dentate gyrus. (A,B) Confocal projections of the dentate gyrus (z-stack of 10 optical sections with 1.7-μm thickness). BrdU, Red; DCX, Blue. Scale bar, 25 μm in (A–D) Confocal image (optical section of 1-μm thickness) of STDSTD in (C) and RUNENR in (D) showing NeuN, Green; BrdU, Red, S100β, Blue; Inset: a, NeuN; b, BrdU; c, S100β. (D) Arrowheads in red indicating colocalization of BrdU and NeuN. Scale bar, 25 μm in (C,D). (E–H) Brightfield images of BrdU-positive cells in the dentate gyrus. Scale bar (in E for E–H), 100 μm.

Figure 3

Figure 3

The number of BrdU-labeled cells in the dentate gyrus was determined along with the cellular phenotypes of BrdU-positive cells (NeuN indicating a neuronal, S100β an astroglial fate). We found RUNSTD to cause an increased number of BrdU-labeled cells as well as new neurons compared to STDSTD. RUNENR resulted in a further increase in the number of BrdU-positive cells and newborn neurons. Therefore, the effects of wheel running and environmental enrichment on adult hippocampal neurogenesis were additive. Fisher post hoc test after ANOVA.

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References

    1. Brandt M. D., Jessberger S., Steiner B., Kronenberg G., Reuter K., Bick-Sander A., von der Behrens W., Kempermann G. (2003). Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Mol. Cell. Neurosci. 24, 603–61310.1016/S1044-7431(03)00207-0 - DOI - PubMed
    1. Dobrossy M. D., Drapeau E., Aurousseau C., Le Moal M., Piazza P. V., Abrous D. N. (2003). Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Mol. Psychiatry 8, 974–98210.1038/sj.mp.4001419 - DOI - PubMed
    1. Ehninger D., Kempermann G. (2006). Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity. Genes Brain Behav. 5, 29–3910.1111/j.1601-183X.2005.00129.x - DOI - PubMed
    1. Fabel K., Kempermann G. (2008). Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromolecular Med. 10, 59–6610.1007/s12017-008-8031-4 - DOI - PubMed
    1. Gould E., Beylin A., Tanapat P., Reeves A., Shors T. J. (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2, 260–26510.1038/6365 - DOI - PubMed

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