{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T09:11:57Z","timestamp":1772183517394,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Circulating white blood cells (WBC) contribute toward maintenance of cerebral metabolism and brain function. Recently, we showed that during aging, transcription of metabolism related genes, including energy source transports, in the brain significantly decreased at the hippocampus resulting in impaired neurological functions. In this article, we investigated the changes in RNA transcription of metabolism related genes (glucose transporter 1 [Glut1], Glut3, monocarboxylate transporter 4 [MCT4], hypoxia inducible factor 1-\u03b1 [Hif1-\u03b1], prolyl hydroxylase 3 [PHD3] and pyruvate dehydrogenase kinase 1 [PDK1]) in circulating WBC and correlated these with brain function in mice. Contrary to our expectations, most of these metabolism related genes in circulating WBC significantly increased in aged mice, and correlation between their increased RNA transcription and impaired neurological functions was observed. Bone marrow mononuclear transplantation into aged mice decreased metabolism related genes in WBC with accelerated neurogenesis in the hippocampus. <jats:italic>In vitro<\/jats:italic> analysis revealed that cell-cell interaction between WBC and endothelial cells via gap junction is impaired with aging, and blockade of the interaction increased their transcription in WBC. Our findings indicate that gross analysis of RNA transcription of metabolism related genes in circulating WBC has the potential to provide significant information relating to impaired cell-cell interaction between WBC and endothelial cells of aged mice. Additionally, this can serve as a tool to evaluate the change of the cell-cell interaction caused by various treatments or diseases.<\/jats:p>","DOI":"10.3389\/fnagi.2022.759159","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:01:04Z","timestamp":1643864464000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Increased RNA Transcription of Energy Source Transporters in Circulating White Blood Cells of Aged Mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Yukiko","family":"Takeuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orie","family":"Saino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Okinaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rie","family":"Akamatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akie","family":"Kikuchi-Taura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosky","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuyo","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheraz","family":"Gul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Claussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Boltze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Taguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s00702-013-1109-7","article-title":"Neuronal gap junction coupling as the primary determinant of the extent of glutamate-mediated excitotoxicity.","volume":"121","author":"Belousov","year":"2014","journal-title":"J. Neural Transm."},{"key":"B2","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/s41573-020-0072-x","article-title":"Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.","volume":"19","author":"Cunnane","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"B3","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nrn.2017.39","article-title":"How and why do T cells and their derived cytokines affect the injured and healthy brain?","volume":"18","author":"Filiano","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1128\/AAC.36.7.1545","article-title":"Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions.","volume":"36","author":"Hill","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.neures.2013.04.001","article-title":"A highly reproducible model of cerebral ischemia\/reperfusion with extended survival in CB-17 mice.","volume":"76","author":"Kasahara","year":"2013","journal-title":"Neurosci. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1002\/stem.3360","article-title":"Gap junction-mediated cell-cell interaction between transplanted mesenchymal stem cells and vascular endothelium in stroke.","volume":"39","author":"Kikuchi-Taura","year":"2021","journal-title":"Stem Cells"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1161\/STROKEAHA.119.028072","article-title":"Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction-Mediated Cell-Cell Interaction.","volume":"51","author":"Kikuchi-Taura","year":"2020","journal-title":"Stroke"},{"key":"B8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1042\/BJ20051922","article-title":"Life cycle of connexins in health and disease.","volume":"394","author":"Laird","year":"2006","journal-title":"Biochem. J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.apsb.2015.05.007","article-title":"HIF-1alpha pathway: role, regulation and intervention for cancer therapy.","volume":"5","author":"Masoud","year":"2015","journal-title":"Acta Pharm. Sin. B."},{"key":"B11","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/s41591-019-0375-9","article-title":"Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer\u2019s disease.","volume":"25","author":"Moreno-Jimenez","year":"2019","journal-title":"Nat. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1749-6632.1986.tb42034.x","article-title":"Methodological considerations for implementation of lymphocyte subset analysis in a clinical reference laboratory.","volume":"468","author":"Muirhead","year":"1986","journal-title":"Ann. N Y. Acad. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"25207","DOI":"10.1074\/jbc.275.33.25207","article-title":"Regulation of connexin degradation as a mechanism to increase gap junction assembly and function.","volume":"275","author":"Musil","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1002\/stem.454","article-title":"Bone marrow mononuclear cells promote proliferation of endogenous neural stem cells through vascular niches after cerebral infarction.","volume":"28","author":"Nakano-Doi","year":"2010","journal-title":"Stem Cells"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1002\/cphy.c110051","article-title":"Gap junctions.","volume":"2","author":"Nielsen","year":"2012","journal-title":"Compr. Physiol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.535902","article-title":"Intravenous Bone Marrow Mononuclear Cells Transplantation Improves the Effect of Training in Chronic Stroke Mice.","volume":"7","author":"Ogawa","year":"2020","journal-title":"Front. Med."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187206","article-title":"Immunohistochemical analysis of PDK1, PHD3 and HIF-1alpha expression defines the hypoxic status of neuroblastoma tumors.","volume":"12","author":"Ognibene","year":"2017","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166168","article-title":"Endothelial connexin-integrin crosstalk in vascular inflammation.","volume":"1867","author":"Okamoto","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.cell.2020.06.026","article-title":"Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition.","volume":"182","author":"Pasciuto","year":"2020","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.bbamem.2012.05.011","article-title":"Connexins in atherosclerosis.","volume":"1828","author":"Pfenniger","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B21","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/jnc.15169","article-title":"Metabolic determinants of leukocyte pathogenicity in neurological diseases.","volume":"158","author":"Runtsch","year":"2020","journal-title":"J. Neurochem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s00441-017-2715-8","article-title":"The systemic environment: at the interface of aging and adult neurogenesis.","volume":"371","author":"Smith","year":"2018","journal-title":"Cell Tissue Res."},{"key":"B23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.6030\/1939-067X-3.1.28","article-title":"A Reproducible and Simple Model of Permanent Cerebral Ischemia in CB-17 and SCID Mice.","volume":"3","author":"Taguchi","year":"2010","journal-title":"J. Exp. Stroke Transl. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1161\/01.CIR.0000133311.25587.DE","article-title":"Circulating CD34-positive cells provide an index of cerebrovascular function.","volume":"109","author":"Taguchi","year":"","journal-title":"Circulation"},{"key":"B25","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1172\/JCI20622","article-title":"Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model.","volume":"114","author":"Taguchi","year":"","journal-title":"J. Clin. Invest."},{"key":"B26","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/sj.jcbfm.9600541","article-title":"Circulating CD34-positive cells provide a marker of vascular risk associated with cognitive impairment.","volume":"28","author":"Taguchi","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00170","article-title":"Intravenous Bone Marrow Mononuclear Cells Transplantation in Aged Mice Increases Transcription of Glucose Transporter 1 and Na(+)\/K(+)-ATPase at Hippocampus Followed by Restored Neurological Functions.","volume":"12","author":"Takeuchi","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.stem.2012.10.011","article-title":"Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells.","volume":"12","author":"Takubo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.stem.2019.05.003","article-title":"Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer\u2019s Disease Patients.","volume":"24","author":"Tobin","year":"2019","journal-title":"Cell Stem Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"7146","DOI":"10.3892\/mmr.2015.4273","article-title":"Connexin 43 expressed in endothelial cells modulates monocyteendothelial adhesion by regulating cell adhesion proteins.","volume":"12","author":"Yuan","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6323901","article-title":"Function of Connexins in the Interaction between Glial and Vascular Cells in the Central Nervous System and Related Neurological Diseases.","volume":"2018","author":"Zhao","year":"2018","journal-title":"Neural. Plast."},{"key":"B32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1365-201X.2004.01380.x","article-title":"Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle.","volume":"183","author":"Zorzano","year":"2005","journal-title":"Acta Physiol. Scand."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.759159\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:01:08Z","timestamp":1643864468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.759159\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":32,"alternative-id":["10.3389\/fnagi.2022.759159"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.759159","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"article-number":"759159"}}