Source Paper
Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice
Klaus Fabel
Frontiers in Neuroscience • 2009
Source Paper
Klaus Fabel
Frontiers in Neuroscience • 2009
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.
Objective: To assess priming effects of running wheel exercise on subsequent enriched environment exposure by comparing hippocampal effects across different temporal sequences of physical activity and environmental enrichment in female mice
This is a Running Wheel Exercise protocol using mouse as the model organism. The procedure involves 6 procedural steps, 3 equipment items, 3 materials. Extracted from a 2009 paper published in Frontiers in Neuroscience.
Model and subjects
mouse • C57BL/6 • female • 8 weeks old at beginning of experiment • 40
Study window
~8 week study window
Core workflow
Animal acquisition and housing setup • Establish experimental groups • Phase 1: First 10-day period
Primary readouts
Key equipment and reagents
Verified items
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Obtain 40 female C57BL/6 mice, 8 weeks old. Randomly distribute to four experimental groups (N = 10 per group). House all animals in same room with constant 12-hour light/dark cycle.
Note: Female mice selected to avoid confounding effects of territorial behavior and social hierarchy in males
“Forty female C57BL/6 mice, 8-weeks old at the beginning of the experiment, were obtained from Charles River (Sulzfeld, Germany). The mice were randomly distributed to four experimental groups, N = 10 per group. All animals were kept in the same room with a constant 12-h-light/dark-cycle”
Create four experimental conditions: (1) RUNENR - running wheel in phase 1, enriched environment in phase 2; (2) RUNSTD - running wheel in phase 1, control conditions in phase 2; (3) STDENR - control conditions in phase 1, enriched environment in phase 2; (4) STDSTD - control conditions in both phases
Note: RUNSTD and RUNENR differ only in phase 2; STDENR and RUNENR differ only in phase 1
“The main experimental group consisted of mice that lived in a cage equipped with a running wheel during the first phase, followed by the exposure to an enriched environment in the second (RUNENR). The first control condition consisted of mice that were running in the first phase but lived under control conditions in the second (RUNSTD). STDENR thus differed only in the first phase, not the second. All three groups were compared to mice living under control conditions (STDSTD).”
Implement first experimental phase lasting 10 days. RUNENR and RUNSTD groups have access to running wheel. STDENR and STDSTD groups remain under control conditions.
Note: Running wheel access is the primary manipulation in phase 1
“The experimental period lasted 45 days, divided into a first phase of 10 days”
At end of first 10-day period, administer single daily injections of BrdU (50 µg/g body weight in 0.9% saline) to five mice from each group for 3 consecutive days
Note: BrdU labels progenitor cells generated in last 3 days of phase 1 to track survival-promoting effects of enrichment in phase 2
“At the end of the first period, five mice of each group received single daily injections of persistent S-phase label bromodeoxyuridine (BrdU; 50 µg/g body weight in 0.9% saline; Sigma) for 3 days”
Implement second experimental phase lasting 35 days. RUNENR group exposed to enriched environment. RUNSTD group remains under control conditions (discontinuation of running wheel). STDENR group exposed to enriched environment. STDSTD group remains under control conditions.
Note: Running wheel access is discontinued for RUNSTD group; measured effects represent sustained effects after 35 days of discontinuation
“a second phase of 35 days. the measured effects of running in this condition represented sustained effects after 35 days of discontinuation of physical exercise”
Analyze all animals at end of 45-day experimental period (10 days phase 1 + 35 days phase 2)
Note: Remaining five mice per group were intended for gene expression study which failed technically
“Because all animals were analyzed at the end of the 45 days. The remaining animals were intended for a gene expression study, which failed technically.”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
To assess priming effects of running wheel exercise on subsequent enriched environment exposure by comparing hippocampal effects across different temporal sequences of physical activity and environmental enrichment in female mice
Objective
To assess priming effects of running wheel exercise on subsequent enriched environment exposure by comparing hippocampal effects across different temporal sequences of physical activity and environmental enrichment in female mice
Subjects
From papermouse • C57BL/6 • female • 8 weeks old at beginning of experiment
Sample count
From paper40
Cohort notes
From paperRandomly distributed to four experimental groups, N = 10 per group.
Animal acquisition and housing setup
Establish experimental groups
Phase 1: First 10-day period (10 days)
BrdU administration at end of phase 1 (3 days)
Hippocampal progenitor cell survival (via BrdU labeling)
From paperNot explicitly described in provided methods text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Priming effects of running wheel on subsequent enrichment exposure
From paperNot explicitly described in provided methods text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Sustained effects of running after 35-day discontinuation
From paperNot explicitly described in provided methods text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Hippocampal progenitor cell survival (via BrdU labeling)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Priming effects of running wheel on subsequent enrichment exposure
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Sustained effects of running after 35-day discontinuation
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not explicitly described in provided methods text
Scoring or quantification
Quantify the primary readouts for this experiment: Hippocampal progenitor cell survival (via BrdU labeling); Priming effects of running wheel on subsequent enrichment exposure; Sustained effects of running after 35-day discontinuation.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Hippocampal progenitor cell survival (via BrdU labeling), Priming effects of running wheel on subsequent enrichment exposure, Sustained effects of running after 35-day discontinuation.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Klaus Fabel (2009). Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Frontiers in Neuroscience
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