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TaggedAPTARAEndTaggedAPTARAFigure Available online at www.sciencedirect.com
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Journal of Sport and Health Science 13 (2024) 245255
Original article
TaggedAPTARAH1Exercised blood plasma promotes hippocampal neurogenesis in the
Alzheimer’s disease rat brainTaggedAPTARAEnd
a
TaggedAPTARAPCecilie Skarstad Norevik a,b,y , Aleksi M. Huuha a,b,y , Ragnhild N. Røsbjørgen ,
c
a
e
Linda Hildegard Bergersen , Kamilla Jacobsen , Rodrigo Miguel-dos-Santos a,d , Liv Ryan ,
f
f,g
a
f,g
Belma Skender , Jose Bianco N. Moreira , Asgeir Kobro-Flatmoen , Menno P. Witter ,
a
Nathan Scrimgeour , Atefe R. Tari a,b, *TaggedAPTARAEnd
a
TaggedAPTARAP Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging,
Norwegian University of Science and Technology, 7491, Trondheim, Norway
b
Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, 7030, Trondheim, Norway
c
Institute of Oral Biology, University of Oslo, 0372, Oslo, Norway
d
Department of Physiology, Federal University of Sergipe, S~ ao Crist ov~ ao, 49100-000, Sergipe, Brazil
e
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine,
Norwegian University of Science and Technology, 7491, Trondheim, Norway
f
Kavli Institute for Systems Neuroscience, Centre for Neural Computation, and Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits,
Norwegian University of Science and Technology, 7030, Trondheim, Norway
g
K.G. Jebsen Centre for Alzheimer’s Disease, Norwegian University of Science and Technology, 7030, Trondheim, Norway
TaggedAPTARAEnd Received 2 December 2022; revised 27 May 2023; accepted 19 June 2023
Available online 25 July 2023
2095-2546/Ó 2024 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license.
(http://creativecommons.org/licenses/by-nc-nd/4.0/)
TaggedAPTARAPAbstract
Background: Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s
disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate
effects of blood plasma from exercise-trained donors on neuronal viability, and an in vivo rat model of AD to test whether such plasma impacts
cognitive function, amyloid pathology, and neurogenesis.
Methods: Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-b and treated with plasma collected from human
male donors 3 h after a single bout of high-intensity exercise. For in vivo studies, blood was collected from exercise-trained young male Wistar
rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic AD rats (McGill-R-Thy1-APP) were injected 5 times/fortnight for 6 weeks at
2 months or 5 months of age with either (a) plasma from the exercise-trained rats, (b) plasma from sedentary rats, or (c) saline. Cognitive func-
tion, amyloid plaque pathology, and neurogenesis were assessed. The plasma used for the treatment was analyzed for 23 cytokines.
Results: Plasma from exercised donors enhanced cell viability by 44.1% (p = 0.032) and reduced atrophy by 50.0% (p < 0.001) in
amyloid-b-treated cells. In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippo-
campal neurogenesis by »3 fold, regardless of pathological stage, when compared to saline-treated rats. Concentrations of 7 cytokines were
significantly reduced in exercised plasma compared to sedentary plasma.
Conclusion: Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote
adult hippocampal neurogenesis in the AD rat brain. This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised
plasma.
TaggedAPTARAPKeywords: Cytokines; High-intensity interval training; Inflammation; Neurons; Plasma transfusionTaggedAPTARAEnd
TaggedAPTARAH11. IntroductionTaggedAPTARAEnd
TaggedAPTARAPDevelopment of Alzheimer’s disease (AD), the most
TaggedAPTARAEndTaggedAPTARAEnd Peer review under responsibility of Shanghai University of Sport. common cause of dementia, is a long process where neuro-
TaggedAPTARAEnd* Corresponding author.
E-mail address: atefe.r.tari@ntnu.no (A.R. Tari). pathological changes may occur up to 20 or more years prior
y 1
TaggedAPTARAEnd Both authors contributed equally to this work. to clinical manifestation. Thus, the typical research approach
https://doi.org/10.1016/j.jshs.2023.07.003
Cite this article: Norevik CS, Huuha AM, Røsbjørgen RN, et al. Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer’s disease rat brain.
J Sport Health Sci 2024;13:24555.