Additional Table 5.

Effects of exercise on glymphatic/neurological activity and the visual system

Exp. Type	Model/Species	Exp. Protocols	Main findings	Citation
in vivo	C57BL/6J mice	° 5 wk voluntary wheel running ° 6 km daily on avg	↑ CSF influx and efflux during wakefulness and when under ketamine-xylazine anesthesia ↓ Glymphatic activity when actively running	von Holstein-Rathlou et al.(2018)
in vivo, in vitro	C57BL/6J, Thy1–GFP transgenic mice	° 6 wk voluntary wheel running ° Assessed via Morris water maze, in vivo two-photon imaging, histology	↓ Time to reach platform in running group ↑ Time spent in target quadrant than control mice ↑ Paravascular CSF-ISF exchange in aging brain ↑ AQP4 polarity in cortex, hippoc., and perivascular regions ↓ Amt of astrocytes and microglia in the cortex, CA1, DG, CA3 regions of hippoc. ↓ Aβ deposition in hippoc. and cortex ↑ Number of dendritic spines in cortex and hippoc.	He et al. (2017)
in vivo, in vitro	APP/PS1 mice	° 10 wk treadmill training at 10-12 m/min for 20-60 min/d ° Assessed via Pavlovian fear conditioning and testing, immunohistochemistry	↓ Body weight gain ↑ Citrate synthase activity in soleus muscles ↑ And restored amyg.-and hippoc.-associated long-and short-term memories ↑ Dendritic complexity and field of the hippoc. and BLA ↑ BDNF signaling pathways and levels of LRP1 in hippoc. and amyg. ↓ Conc of Aβ in hippoc. and amyg.	Lin et al. (2015)
in vivo, in vitro	Sprague-Dawley rats	° 2.4 mg/kg STZ bilateral ICV injection for AD rat model ° 4 wk treadmill exercise of 30 min/d, 5 d/wk at 1 wk post-STZ ° Assessed via Barnes maze task, passive avoidance test, novel object recognition test, immunohistochemistry, histology	↑ And restored memory function and novel object recognition ability ↓ Latency in completing tasks ↓ STZ-induced hippoc. neuronal degeneration ↓ Levels of Aβ, AβPP amyloidogenic processing, hyperphosphorylation of tau protein in hippoc. regions ↑ Anti-inflammatory cytokine (IL-4, IL-10) levels ↓ Pro-inflammatory cytokine (IL-1β, TNF-α) levels ↓ Neuronal damage by oxidative stress and caspase activity ↑ CCO activity and ATP production	Lu et al. (2017)
in vivo	Humans	° 5 yr study ° Exercise frequency and period varied ° IOP measured at beginning and end of study	° More frequent exercise per week and longer exercise time significantly associated with greater decrease in IOP	Fujiwara et al. (2019)
in vivo	Humans	° Yoga positions (Adho Mukha Svanasana, Uttanasana, Halasana, Viparita Karani) held for 2 min each ° IOP measured before, during, and after the exercises	↑ IOP during yoga poses w/in 2 min, greatest increase in Adho Mukha Svanasana position ↓ IOP to baseline after poses in seated position ° Glaucoma pts had IOPs 1-2 mmHg higher on avg compared to controls but not statistically significant	Jasien et al. (2015)
in vivo	Glaucoma patients	° Pts of ages 60-80 yr wore accelerometers for 1 wk ° Assessed via Humphrey VF at baseline and 1 wk	↓ VF sensitivity ∝↑ daily steps and non-sedentary activity ° Covariates associated with faster sensitivity loss include age, non-Caucasian race, h/o glaucoma or cataract surgery, worse VF loss at baseline	Lee et al. (2019b)

Aβ: Amyloid-beta, AβPP: amyloid-beta precursor protein, AD: Alzheimer’s disease, AQP4: aquaporin-4, ATP: adenosine triphosphate, BDNF: brain-derived neurotrophic factor, BLA: basolateral amygdala, CCO: cytochrome c oxidase, CSF: cerebrospinal fluid, DG: dentate gyrus, ICV: intracerebroventricular, IL: interleukin, IOP: intraocular pressure, ISF: interstitial fluid, LRP1: low density lipoprotein receptor-related protein 1, STZ: streptozotocin, TNF-α: tumor necrosis factor alpha, VF: visual field.