Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Microglia and Cytokines in a Transgenic Rat Model of Alzheimer's Disease.

Autor:	Huuha AM; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Norevik CS; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Coombes JS; Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Australia., Røsbjørgen RN; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Miguel-Dos-Santos R; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Physiology, Federal University of Sergipe, Sergipe, Brazil., Moreira JBN; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Kobro-Flatmoen A; 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, Trondheim, Norway.; K.G. Jebsen Centre for Alzheimer's Disease, Norwegian University of Science and Technology, Trondheim, Norway., Scrimgeour N; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Tari AR; Department of Circulation and Medical Imaging, Cardiac Exercise Research Group (CERG), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Jazyk:	angličtina
Zdroj:	Brain plasticity (Amsterdam, Netherlands) [Brain Plast] 2024 May 14; Vol. 9 (1-2), pp. 21-41. Date of Electronic Publication: 2024 May 14 (Print Publication: 2024).
DOI:	10.3233/BPL-230154
Abstrakt:	Background: Microglia and inflammation play a significant role in Alzheimer's disease (AD). Physical exercise and peripheral signals can influence microglial activity in the brain. Modulating the inflammatory response in the brain may provide therapeutic approaches for AD. Objective: To assess the effects of intravenously administered blood plasma from exercise-trained donor rats on cognitive function, microglia, and cytokine levels in an AD rat model at two different pathological stages; an early pre-plaque stage and a later stage closer to the emergence of extracellular plaques. Methods: Male transgenic McGill-R-Thy1-APP rats aged 2 and 5 months received 14 injections over 6 weeks: 1) plasma from exercise-trained rats (ExPlas), 2) plasma from sedentary rats (SedPlas), or 3) saline. Cognitive function was evaluated in a novel object recognition task. Microglia count and morphology were analyzed in cornu ammonis, dentate gyrus, entorhinal cortex, and subiculum. Amyloid plaque number and size were assessed in the rats with the later treatment start. A multiplex assay was used to measure 23 cytokines in cornu ammonis. Results: In rats treated from 2 months of age, ExPlas and SedPlas increased number and length of microglial branches in cornu ammonis and dentate gyrus compared to saline. Only ExPlas-treated rats exhibited similar changes in subiculum, while entorhinal cortex showed no differences across treatments. Microglia count remained unaffected. In rats treated from 5 months of age, there were no significant differences in microglia count or morphology or the number or size of amyloid plaques in any brain region. Compared to both other treatments in early pre-plaque stage rats, SedPlas increased TNF-α levels. ExPlas upregulated GM-CSF, IL-18, and VEGF, while SedPlas increased IL-10 compared to saline. In later-stage rats, ExPlas upregulated IL-17, and SedPlas upregulated TNF-α compared to saline. There were no effects of treatments on recognition memory. Conclusions: Intravenous injections of blood plasma from exercise-trained and sedentary donors differentially modulated microglial morphology and cytokine levels in the AD rat model at an early pre-plaque stage of pathology. Exercised plasma may reduce proinflammatory TNF-α signaling and promote microglial responses to early Aβ accumulation but the lack of treatment effects in the later-stage rats emphasizes the potential importance of treatment timing. Competing Interests: The authors have no conflict of interest to report. (© 2024 – The authors. Published by IOS Press.)
Databáze:	MEDLINE
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