Page 124 - 《运动与健康科学》(英文)2024年第2期

TaggedAPTARAEnd246 C.S. Norevik et al.
of implementing treatments following clinical manifestation effects of exercise can be transferred through plasma injections
might be ineffective for AD as, by this stage, too much neural causing increased hippocampal neurogenesis and improved
5
damage may have ensued. If correct, this scenario helps cognitive function, potentially through downregulation of
6
explain why AD drug candidates have one of the highest inflammatory signaling. Previously, only a single study has
failure rates of any disease area. 1 This has led some examined the effect of exercised blood in the context of an AD
researchers to shift their focus towards prevention by modifi- rodent brain, showing that blood plasma from exercise-trained
able risk factors. A leading hypothesis is that the incidence of young mice, when infused into the triple transgenic AD mouse
AD and dementia may be reduced substantially (30%50%) model, increased hippocampal neurogenesis, improved mito-
through modifiable cardiovascular risk factors, such as by chondrial function, and reduced expression of cell death
increased physical activity and increased age-specific cardiore- markers, seemingly leading to improved spatial learning and
spiratory fitness. 24 TaggedAPTARAEnd memory performance. 24 As there is no ideal AD model to
TaggedAPTARAPHuman and rodent studies have shown that exercise mimic human AD, it is important to expand upon previous
enhances blood delivery to the brain and induces molecular research by examining the potential treatment effects of exer-
changes in blood which seem to mediate some of the neurolog- cised plasma at different stages of AD development in several
ical beneficial effects of exercise, 57 as reviewed. 4,8 Studies in relevant AD models. Here, we expand upon this knowledge by
rodents have shown exercise to decrease inflammation in the studying the effects of exercised blood in vitro and in vivo.TaggedAPTARAEnd
912
brain and increase hippocampal neurogenesis, partly TaggedAPTARAPFirst, we tested the potential effect of exercised plasma in a
10,11,13
reversing the age-dependent reduction in cognition. hippocampal neuronal cells (HT22) culture model of AD. We
Neural stem cells that give rise to new neurons in the hippo- further tested the potential preventive and therapeutic effects
campal dentate gyrus are located around blood vessels 14 and of exercised plasma administration in a transgenic rat model of
proliferate in response to vascular growth factors, 14,15 which AD at 2 different stages of AD development. Our hypotheses
indicates that exercise-induced increases in cerebral blood were that (a) plasma from exercised donors would protect the
flow may contribute to improving the communication between HT22 cell model against AD-like damage, and (b) exercised
the systemic environment and the neurogenic niche. 16 In line plasma transfusions would promote adult hippocampal neuro-
with this, studies in mice show that cognitive impairment and genesis and cognitive function in the AD rats at an early pre-sym-
age-related decline in neurogenesis can partially be attributed ptomatic stage but not at a later symptomatic stage.TaggedAPTARAEnd
to changes in blood-borne factors. 16,17 Notably, adult hippo-
campal neurogenesis also drops sharply in human subjects TaggedAPTARAH12. MethodsTaggedAPTARAEnd
with AD compared to healthy controls, 18 which suggests that
TaggedAPTARAH22.1. Human donors and cell cultureTaggedAPTARAEnd
hippocampal neurogenesis is a potential therapeutic target.TaggedAPTARAEnd
TaggedAPTARAPSystemic administration of blood from young to old mice TaggedAPTARAPPlasma was collected from 4 healthy young men (maximal
has been shown to have beneficial effects as far as counterac- oxygen uptake = 63.2 § 3.1 mL/min/kg, age = 27 § 4 years;
ting age-related degeneration in the brains of old mice, while mean § SD). Donors performed a single high-intensity
blood from old mice administered into young mice conversely interval treadmill exercise session consisting of a 10-min
has detrimental effects. 17,19 The beneficial effect of young warm-up, 4 times 4-min intervals (reaching »90% of maximal
blood administration into old animals appears to have a broad heart rate) separated by 3 min of active recovery at 50%70%
impact, increasing hippocampal spine density, synaptic plas- peak heart rate, and a 5-min cool-down. Blood was collected
ticity, blood flow, and neurogenesis, which results in improved before exercise (resting plasma) and at different time points
17,1921
hippocampal-dependent learning and memory. The after a bout of exhaustive high intensity exercise (0 h, 1 h, 3 h,
first clinical trial involving transfusion of plasma from young 6 h, and 24 h) (exercised plasma).TaggedAPTARAEnd
donors to subjects with mild cognitive impairment or early AD TaggedAPTARAPCultured HT22 mouse hippocampal neuronal cells were
found it to be safe and possibly beneficial as exploratory used to test whether exercised plasma induces any protective
endpoint analysis indicated improvements in functional abili- effects on the cells. The HT22 mouse neuronal cell line was
ties. 22 Taken together, the abovementioned studies indicate provided by Richard Dargusch, Cellular Neurobiology Labora-
that systemic manipulation may have wide-ranging rejuve- tory (CNB-S) at The Salk Institute (San Diego, CA, USA). The
nating and therapeutic effects, and they suggest that targeting HT22 cells were cultured at 37˚C in 5% CO 2 in air in
the systemic environment may potentially be an effective Dulbecco’s modified Eagle medium supplemented with 10%
strategy for preventing neurodegeneration and maintaining fetal bovine serum and 50 U/mL penicillin/streptomycin.
neurogenesis in the AD brain. Systemically delivering the Colorimetric MTS ((3-4,5-dimethylthiazol-2-yl)-5-(3-carbox-
exercise effects to individuals with limited ability to perform ymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cell
high-intensity exercise may thus present a novel approach for proliferation assay (CellTiter 96; Promega, Fitchburg, WI,
USA) was then performed in different experimental settings,
AD therapy.TaggedAPTARAEnd
TaggedAPTARAPA few studies have reported finding a causal link between including in HT22 cells that were (a) untreated controls, (b)
exercise-induced circulating factors and exercise-like adapta- treated with human plasma collected prior to exercise or 0 h, 1 h,
tions in organs not subjected to the exercise stimulus. These 3 h, 6 h, and 24 h post-exercise, (c) treated with amyloid-b (Ab),
reports indicate that a protective exercise-induced effect may or (d) co-treated with Ab and human plasma collected prior to
be induced by blood-borne molecules. 23 Such beneficial exercise or 0 h, 1 h, 3h, 6 h, and 24 h post-exercise.TaggedAPTARAEnd