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Neurosci Lett. 2018 Jan 1;662:253-258. doi: 10.1016/j.neulet.2017.10.035. Epub 2017 Oct 25.

Voluntary running enhances glymphatic influx in awake behaving, young mice.

Author information

1
Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: nedergaard@sund.ku.dk.
2
Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark.
3
Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark; Center for Translational Neuromedicine, Division of Glial Disease and Therapeutics, University of Rochester Medical Center, Rochester, New York 14642, USA.

Abstract

Vascular pathology and protein accumulation contribute to cognitive decline, whereas exercise can slow vascular degeneration and improve cognitive function. Recent investigations suggest that glymphatic clearance measured in aged mice while anesthetized is enhanced following exercise. We predicted that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We injected fluorescent tracers in cisterna magna of awake behaving mice and in ketamine/xylazine anesthetized mice, and later assessed tracer distribution in coronal brain sections. Voluntary exercise consistently increased CSF influx during wakefulness, primarily in the hypothalamus and ventral parts of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas of the mouse brain, which may contribute to the pro-cognitive effects of exercise.

KEYWORDS:

Astrocyte; Cardiovascular changes; Convection; Exercise; Glymphatic system; Hypothalamus

PMID:
29079431
PMCID:
PMC5696653
[Available on 2019-01-01]
DOI:
10.1016/j.neulet.2017.10.035
[Indexed for MEDLINE]

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