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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.
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