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elevated risk of developing the disease among individuals
carrying the APOE-ε 4 allele—the most common gene variant
linked with late onset of the disease. And more-recent stud-
ies suggest exercise can combat brain deterioration associ-
ated with the disease.
In 2018, van Praag, along with researchers from Harvard
Medical School, MIT, Massachusetts General Hospital, the
Dana-Farber Cancer Institute, and the Salk Institute, published
a mouse study that found that neither a neuroprotective drug
nor a gene therapy to overproduce WNT3, a protein that has
been linked to neurogenesis, reversed signs of dementia. Ye t ,
when the mice were allowed to exercise, their cognitive perfor-
mance improved. When the team combined the neuroprotective
drug with treatments to overexpress the Bdnf gene in the brains
of mice that didn’t exercise, improvements in their cognitive per-
formance matched those of the mice that were given access to a
running wheel.^10 The work, van Praag says, may provide avenues
toward treating patients with neurodegenerative diseases who
are too frail to exercise.
The result also offers support for the 58 clinical trials currently
being done on exercise, cognition, and Alzheimer’s disease. There
are nearly 100 ongoing trials, including Petzinger’s, investigat-
ing exercise’s role in easing Parkinson’s symptoms, and hundreds
more looking at exercise as an intervention against depression.
Some researchers are even testing the effects of exercise on aging.
“A n active lifestyle is not going to turn a 70-year-old brain
into a 30-year-old brain,” says Petzinger. “But studying exercise’s
effect on the nervous system could help researchers identify the
best and most efficient strategy—whether it’s activity alone or
activity paired with drugs—to maintain brain health as we age.” gReferences- H. Maejima et al., “Exercise and low-level GABAA receptor inhibition
modulate locomotor activity and the expression of BDNF accompanied
by changes in epigenetic regulation in the hippocampus,” Neurosci Lett,
685:18–23, 2018. - H. van Praag et al., “Running increases cell proliferation and neurogenesis in
the adult mouse dentate gyrus,” Nat Neurosci, 2:266–70, 1999.
3. H. van Praag et al., “Running enhances neurogenesis, learning, and long-term
potentiation in mice,” PNAS, 96:13427–31, 1999.
4. A. Collins et al., “Exercise improves cognitive responses to psychological stress
through enhancement of epigenetic mechanisms and gene expression in the
dentate gyrus,” PLOS ONE, 4:e4330, 2009.
5. S.F. Sleiman et al., “Exercise promotes the expression of brain derived
neurotrophic factor (BDNF) through the action of the ketone body
β-hydroxybutyrate,” eLife, 5:e15092, 2016. - H.Y. Moon et al., “Running-induced systemic cathepsin B secretion is
associated with memory function,” Cell Metab, 24:332–40, 2016. - B.E. Fisher et al., “Exercise-induced behavioral recovery and neuroplasticity
in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–lesioned mouse basal
ganglia,” J Neuro Res, 77:378–90, 2004. - B.E. Fisher et al., “Treadmill exercise elevates striatal dopamine D2 receptor
binding potential in patients with early Parkinson’s disease,” NeuroReport,
24:509–14, 2013. - W.A. To y et al., “Treadmill exercise reverses dendritic spine loss in direct and
indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) mouse model of Parkinson’s disease,” Neurobiol
Dis, 63:201–09, 2014. - S.H. Choi et al., “Combined adult neurogenesis and BDNF mimic
exercise effects on cognition in an Alzheimer’s mouse model,” Science,
361:eaan8821, 2018.
Studying exercise’s effect
on the nervous system could
help researchers identify
the best and most efficient
strategy to maintain brain
health as we age.
—Giselle Petzinger, University of Southern California