{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:23:09Z","timestamp":1787563389533,"version":"build-2736575974"},"reference-count":53,"publisher":"IOS Press","issue":"1-2","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Brain Plasticity"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Microglia and inflammation play a significant role in Alzheimer\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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-\u03b1 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-\u03b1 compared to saline. There were no effects of treatments on recognition memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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-\u03b1 signaling and promote microglial responses to early A\u03b2 accumulation but the lack of treatment effects in the later-stage rats emphasizes the potential importance of treatment timing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/bpl-230154","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:39:02Z","timestamp":1715341142000},"page":"21-41","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Microglia and Cytokines in a Transgenic Rat Model of Alzheimer\u2019s Disease"],"prefix":"10.3233","volume":"9","author":[{"given":"Aleksi M.","family":"Huuha","sequence":"first","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]},{"name":"Trondheim University Hospital","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilie Skarstad","family":"Norevik","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]},{"name":"Trondheim University Hospital","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff S.","family":"Coombes","sequence":"additional","affiliation":[{"name":"The University of Queensland","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhild N.","family":"R\u00f8sbj\u00f8rgen","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Miguel-dos-Santos","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]},{"name":"Federal University of Sergipe","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Bianco N.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asgeir","family":"Kobro-Flatmoen","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]},{"name":"Norwegian University of Science and Technology","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Scrimgeour","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-5255","authenticated-orcid":false,"given":"Atefe R.","family":"Tari","sequence":"additional","affiliation":[{"name":"Norwegian University of Science and Technology","place":["Norway"]},{"name":"Trondheim University Hospital","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7437","published-online":{"date-parts":[[2024,5]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.053"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110647"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4814-07.2008"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914593117"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz2288"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20531"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101559"},{"issue":"5","key":"e_1_3_5_12_2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/mp.2014.114","article-title":"Vascular hippocampal plasticity afteraerobic exercise in older adults","volume":"20","author":"Maass A","year":"2015","unstructured":"MaassA D\u00fczelS GoerkeM BeckeA SobierayU NeumannK, et al. Vascular hippocampal plasticity afteraerobic exercise in older adults. Mol Psychiatry. 2015;20(5):585\u201393.","journal-title":"Mol Psychiatry"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015950108"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1731-05.2005"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611721104"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.06.002"},{"key":"e_1_3_5_17_2","first-page":"78","article-title":"Treadmill exercise decreases A\u03b2 deposition andcounteracts cognitive decline in APP\/PS1 mice, possibly via hippocampal microglia modifications","volume":"11","author":"Zhang X","year":"2019","unstructured":"ZhangX HeQ HuangT ZhaoN LiangF XuB, et al. Treadmill exercise decreases A\u03b2 deposition andcounteracts cognitive decline in APP\/PS1 mice, possibly via hippocampal microglia modifications. Front AgingNeurosci. 2019;11:78.","journal-title":"Front AgingNeurosci"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-022-00534-2"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04183-x"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2019.02.003"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10357"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3569"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw2622"},{"issue":"9","key":"e_1_3_5_24_2","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.3390\/ijms21093291","article-title":"Infusion of plasma from exercised mice ameliorates cognitive dysfunction byincreasing hippocampal neuroplasticity and mitochondrial functions in 3\u00d7Tg-AD mice","volume":"21","author":"Kim TW","year":"2020","unstructured":"KimTW ParkSS ParkJY ParkHS. Infusion of plasma from exercised mice ameliorates cognitive dysfunction byincreasing hippocampal neuroplasticity and mitochondrial functions in 3\u00d7Tg-AD mice. Int J Mol Sci. 2020;21(9):3291.","journal-title":"Int J Mol Sci"},{"key":"e_1_3_5_25_2","unstructured":"NorevikCS HuuhaAM R\u00f8sbj\u00f8rgenRN BergersenL JacobsenK Miguel-dos-SantosR et al. Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer\u2019s disease rat brain. Journal of Sport and Health Science. 2023."},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1349"},{"key":"e_1_3_5_27_2","unstructured":"Annelise HemDME Espen Engh & Adrian Smith. Laboratory Animal Science. 2001."},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10339-011-0430-z"},{"key":"e_1_3_5_29_2","unstructured":"PaxinosG WatsonC. The rat brain : In stereotaxic coordinates. Compact 6th ed. ed. Amsterdam: Elsevier\/AP; 2009."},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_5_31_2","doi-asserted-by":"crossref","unstructured":"YoungK MorrisonH. Quantifying microglia morphology from photomicrographs of immunohistochemistry prepared tissue using imageJ. J Vis Exp. 2018(136).","DOI":"10.3791\/57648-v"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20829"},{"key":"e_1_3_5_33_2","doi-asserted-by":"crossref","unstructured":"HovensI NyakasC SchoemakerR. A novel method for evaluating microglial activation using ionized calciumbinding adaptor protein-1 staining: Cell body to cell size ratio. Neuroimmunology and Neuroinflammation. 2014: 82-8.","DOI":"10.4103\/2347-8659.139719"},{"key":"e_1_3_5_34_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s40478-014-0175-x","article-title":"Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human A\u00df-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: Rapid reversal by anti-A\u00dfagents","volume":"2","author":"Qi Y","year":"2014","unstructured":"QiY KlyubinI HarneySC HuN CullenWK GrantMK, et al. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human A\u00df-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: Rapid reversal by anti-A\u00dfagents. Acta Neuropathol Commun. 2014;2:175.","journal-title":"Acta Neuropathol Commun"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.03.026"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1922-z"},{"issue":"1","key":"e_1_3_5_37_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1523\/JNEUROSCI.1698-16.2016","article-title":"Large Soluble Oligomers of Amyloid \u03b2-Protein from AlzheimerBrain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate","volume":"37","author":"Yang T","year":"2017","unstructured":"YangT LiS XuH WalshDM SelkoeDJ. Large Soluble Oligomers of Amyloid \u03b2-Protein from AlzheimerBrain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate. J Neurosci. 2017;37(1):152\u201363.","journal-title":"J Neurosci"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.12.002"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00438-z"},{"issue":"1","key":"e_1_3_5_40_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13195-019-0498-8","article-title":"Peripheraladministration of human recombinant ApoJ\/clusterin modulates brain beta-amyloid levels in APP23 mice","volume":"11","author":"de Retana SF","year":"2019","unstructured":"de RetanaSF MarazuelaP Sol\u00e9M ColellG BonaterraA S\u00e1nchez-QuesadaJL, et al. Peripheraladministration of human recombinant ApoJ\/clusterin modulates brain beta-amyloid levels in APP23 mice. AlzheimersRes Ther. 2019;11(1):42.","journal-title":"AlzheimersRes Ther"},{"issue":"4","key":"e_1_3_5_41_2","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/glia.23505","article-title":"Unique role for dentate gyrus microglia in neuroblast survival and in VEGF-induced activation","volume":"67","author":"Kreisel T","year":"2019","unstructured":"KreiselT WolfB KeshetE LichtT. Unique role for dentate gyrus microglia in neuroblast survival and in VEGF-induced activation. Glia. 2019;67(4):594\u2013618.","journal-title":"Glia"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.08.014"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088417"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302229"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694591"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.4.538"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.09.013"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-091471"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2003.03041.x"},{"key":"e_1_3_5_50_2","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1038\/ncomms15557","article-title":"Exercise induces cerebral VEGF andangiogenesis via the lactate receptor HCAR1","volume":"8","author":"Morland C","year":"2017","unstructured":"MorlandC AnderssonKA Haugen\u00d8P HadzicA KleppaL GilleA, et al. Exercise induces cerebral VEGF andangiogenesis via the lactate receptor HCAR1. Nat Commun. 2017;8:15557.","journal-title":"Nat Commun"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.10.027"},{"issue":"17","key":"e_1_3_5_52_2","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1016\/j.febslet.2014.05.046","article-title":"Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis","volume":"588","author":"Neniskyte U","year":"2014","unstructured":"NeniskyteU VilaltaA BrownGC. Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis. FEBS Lett. 2014;588(17):2952\u20136.","journal-title":"FEBS Lett"},{"issue":"6523","key":"e_1_3_5_53_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/374647a0","article-title":"Activation of microglial cells by beta-amyloid protein and interferon-gamma.","volume":"374","author":"Meda L","year":"1995","unstructured":"MedaL CassatellaMA SzendreiGI OtvosLJr. BaronP. VillalbaM., et al. Activation of microglial cells by beta-amyloid protein and interferon-gamma.. Nature. 1995;374(6523):647\u201350.","journal-title":"Nature"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060378"}],"container-title":["Brain Plasticity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/BPL-230154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/BPL-230154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/BPL-230154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:34:23Z","timestamp":1777383263000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/BPL-230154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":53,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.3233\/BPL-230154"],"URL":"https:\/\/doi.org\/10.3233\/bpl-230154","relation":{},"ISSN":["2213-6304","2213-6312"],"issn-type":[{"value":"2213-6304","type":"print"},{"value":"2213-6312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]}}}