Page 131 - 《运动与健康科学》(英文)2024年第2期

TaggedAPTARAEndExPlas promotes neurogenesis in AD rat brain 253
sessions per week. 41 The number of injections per week and in TaggedAPTARAH24.5. Limitations and strengthsTaggedAPTARAEnd
total might therefore have been too low to result in a signifi-
TaggedAPTARAPA major strength of this study is that all experiments and
cant effect in our study. Two studies examining young blood
analyses were conducted while blinded to the treatment alloca-
transfusion effects on amyloid pathology in AD mouse models
tion of AD rats. This study has several limitations. First, we
have also reported reduction in amyloid plaques following 4 or only analyzed cytokine levels in the rat donor plasma, and not
8 weeks of treatment. 20,21 In these studies, the recipients of
in the human plasma used to treat the HT22 cells. Second,
young blood were aged mice with advanced plaque pathology.
although we included approximately the same number of
Therefore, the greater age difference between blood donors 24
animals as were included in a comparable pre-clinical study,
and recipients might be reflected in the molecular composition
our sample is small, which is why we suggest this be regarded
of the blood, resulting in more profound effects. On the other
as a proof-of-concept study that may help form the basis for
hand, our results might simply reflect individual differences,
future studies with larger sample sizes. Another potential limi-
in which case a larger number of samples could better account
tation is the length of the treatment period. Further studies are
for the variation in the emergence of plaques. Even so, a study
needed to explore whether a longer treatment period could
with heterochronic parabiosis of old AD mice joined to young
result in an even stronger treatment effect with respect to
wild type mice found no effect on amyloid pathology from
42 neurogenesis, and potentially cognitive function and amyloid
young blood exposure. TaggedAPTARAEnd
pathology as well. One should also consider whether a plasma
exchange protocol (removing a given amount of plasma equiv-
alent to the volume injected) would be an even better treatment
approach. Furthermore, as many as 213 different AD animal
TaggedAPTARAH24.4. NeurogenesisTaggedAPTARAEnd
models are available 45 and, therefore, we cannot rule out that
TaggedAPTARAPOur results suggest a positive effect of ExPlas treatment on
other models may be more suitable and reflect human AD
hippocampal neurogenesis, independent of the treatment
better than the model used here. Future studies should examine
timing in relation to the stage of AD pathology, hence
all these factors as well as study the potential undiscovered
strengthening existing evidence that exercise-induced changes
molecular effects of exercise training and high cardiorespira-
in blood can serve as potent mediators of hippocampal tory fitness that might reduce the risk of or even have thera-
neurogenesis. 5,6 A study in triple-transgenic AD mice found
peutic effects on AD.TaggedAPTARAEnd
similarly that exercised plasma treatment promoted hippo-
campal neurogenesis in the aged AD mice compared to
untreated controls. 24 Together these findings indicate that TaggedAPTARAH15. ConclusionTaggedAPTARAEnd
there are exercise-induced changes in plasma that confer bene- TaggedAPTARAPThe present study demonstrates that blood plasma from
exercise-trained donors can promote neuronal viability and
ficial effects on hippocampal neurogenesis in AD models.TaggedAPTARAEnd
TaggedAPTARAPPrevious studies have suggested the upregulation of neuro- potently enhance adult hippocampal neurogenesis, but with
protective molecules such as BDNF may mediate the effects limited effect on cognitive function. The reduced levels of
of exercise and exercised plasma transfusions on pro-inflammatory cytokines in plasma from exercise-trained
neurogenesis. 5,6,24 However, our analysis of ExPlas and donor rats provide evidence to suggest the effects of exercise
SedPlas showed no differences in BDNF levels, suggesting training on the brain are at least partly mediated by blood-
that donor plasma BDNF content plays no role in the observed borne factors.TaggedAPTARAEnd
neurogenesis effects. On the other hand, exercise and exercised
plasma transfusion may counteract the adverse effects of TaggedAPTARAH1AcknowledgmentsTaggedAPTARAEnd
inflammation and AD pathology on the hippocampal neuro-
6,43 TaggedAPTARAPThe HT22 mouse neuronal cell line was provided by
genic niche and neural stem cells. Our results are in line
Richard Dargusch, Cellular Neurobiology Laboratory (CNB-S)
with these findings, showing significantly reduced levels of
at The Salk Institute (San Diego, CA, USA). We also want to
several pro-inflammatory cytokines in ExPlas compared to
thank Grethe Mari Olsen and Bruno Monterotti for helping
SedPlas. For example, the monocyte chemoattractant protein-1
with brain tissue processing, Knut Sverre Grøn for assistance
(MCP-1), also referred to as chemokine ligand 2 (CCL2),
with intravenous injections, and Laia Casas Manzanal for
which was significantly downregulated (21%) in ExPlas, has
assistance with BDNF enzyme-linked immunosorbent assay.
previously been found to be correlated with aging-associated The study was funded by The Norwegian Research Council,
decline in neurogenesis. 16 As both aging and AD are associ-
the Liaison Committee between the Central Norway Regional
ated with upregulation of inflammatory molecules in plasma Health Authority, and NTNU. RMS was funded by the Coordi-
and in cerebrospinal fluid, 44 treatment of the later-stage AD
nation for the Improvement of Higher Education Personnel-
rats with young donor plasma might have been expected to
Brazil (Capes).TaggedAPTARAEnd
result in greater effects than treatment of the early-stage rats of
similar age as the donors. Still, we found remarkably similar
TaggedAPTARAH1Authors’ contributionsTaggedAPTARAEnd
magnitude effects for both ExPlas and SedPlas treatments on
neurogenesis in early-stage and later-stage AD rats as TaggedAPTARAPCSN participated in the cell study, planning and carrying
compared to those who received the corresponding control out of the animal study and the amyloid plaque staining, and
drafted the manuscript; AMH participated in the animal study,
saline treatments.TaggedAPTARAEnd