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Voluntary running enhances glymphatic influx in awake behaving, young mice
Open accessAbstract
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.
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Glymphatic flow is partly active in quiet wakefulness, whereas active wakefulness potently suppresses CSF inflow.
“glymphatic flow is partly active in quiet wakefulness, whereas active wakefulness potently suppresses CSF inflow88.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [88]
The Results (‘Regional fluorescence intensity differs’; page unavailable) show CSF tracer uptake in awake mice. The Results (‘Wheel running impairs tracer influx’; page unavailable) report that acute running suppressed influx relative to awake behaving, exercised mice. The paper does not establish that the comparator was in quiet wakefulness or that active wakefulness generally suppresses inflow; it tests running specifically. (LLM, conf=0.84)
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Self-citationNorepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep
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Self-citation
Metadata
- Authors
- von Holstein-Rathlou, S., Petersen, N. C., & Nedergaard, M.
- Affiliations
- University of Copenhagen (DK)
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 662
- Pages
- 253-258
- ISSN
- 0304-3940 (ISSN-L)
- PMC
- PMC5696653
- OpenAlex
- W2766767654
- Cited by
- 147
- References
- 7
- Citations by year
- 2026: 30 · 2025: 25 · 2024: 18 · 2023: 24 · 2022: 13 · 2021: 12 · 2020: 6 · 2019: 9 · 2018: 10
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neuroscience Letters (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Læge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat
- Novo Nordisk Fonden
- National Institutes of Health
- Lundbeckfonden
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- glymphatic system, voluntary wheel running, CSF clearance, physical activity, awake behaving mice, hypothalamus, cerebral cortex, cognitive decline
- MeSH terms
- Animals, Brain, Cerebrospinal Fluid, Female, Mice, Inbred C57BL, Physical Conditioning, Animal, Wakefulness, Mice
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