{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:00:45Z","timestamp":1790992845148,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PSG471"],"award-info":[{"award-number":["PSG471"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["SJD90"],"award-info":[{"award-number":["SJD90"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["2014-2020.4.01.15-0012"],"award-info":[{"award-number":["2014-2020.4.01.15-0012"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund","award":["PSG471"],"award-info":[{"award-number":["PSG471"]}]},{"name":"European Regional Development Fund","award":["SJD90"],"award-info":[{"award-number":["SJD90"]}]},{"name":"European Regional Development Fund","award":["2014-2020.4.01.15-0012"],"award-info":[{"award-number":["2014-2020.4.01.15-0012"]}]},{"name":"CELSA","award":["PSG471"],"award-info":[{"award-number":["PSG471"]}]},{"name":"CELSA","award":["SJD90"],"award-info":[{"award-number":["SJD90"]}]},{"name":"CELSA","award":["2014-2020.4.01.15-0012"],"award-info":[{"award-number":["2014-2020.4.01.15-0012"]}]},{"name":"Eye Hope Foundation","award":["PSG471"],"award-info":[{"award-number":["PSG471"]}]},{"name":"Eye Hope Foundation","award":["SJD90"],"award-info":[{"award-number":["SJD90"]}]},{"name":"Eye Hope Foundation","award":["2014-2020.4.01.15-0012"],"award-info":[{"award-number":["2014-2020.4.01.15-0012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Biallelic mutations in the gene encoding WFS1 underlie the development of Wolfram syndrome (WS), a rare neurodegenerative disorder with no available cure. We have previously shown that Wfs1 deficiency can impair the functioning of the renin-angiotensin-aldosterone system (RAAS). The expression of two key receptors, angiotensin II receptor type 2 (Agtr2) and bradykinin receptor B1 (Bdkrb1), was downregulated both in vitro and in vivo across multiple organs in a rat model of WS. Here, we show that the expression of key RAAS components is also dysregulated in neural tissue from aged WS rats and that these alterations are not normalized by pharmacological treatments (liraglutide (LIR), 7,8-dihydroxyflavone (7,8-DHF) or their combination). We found that the expression of angiotensin II receptor type 1a (Agtr1a), angiotensin II receptor type 1b (Agtr1b), Agtr2 and Bdkrb1 was significantly downregulated in the hippocampus of WS animals that experienced chronic experimental stress. Treatment-na\u00efve WS rats displayed different gene expression patterns, underscoring the effect of prolonged experiment-induced stress. Altogether, we posit that Wfs1 deficiency disturbs RAAS functioning under chronic stressful conditions, thereby exacerbating neurodegeneration in WS.<\/jats:p>","DOI":"10.3390\/genes14040827","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T03:17:35Z","timestamp":1680146255000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chronic Stress Alters Hippocampal Renin-Angiotensin-Aldosterone System Component Expression in an Aged Rat Model of Wolfram Syndrome"],"prefix":"10.3390","volume":"14","author":[{"given":"Marite","family":"Punapart","sequence":"first","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riin","family":"Reimets","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadri","family":"Seppa","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"},{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Kirillov","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayana","family":"Gaur","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kattri-Liis","family":"Eskla","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toomas","family":"Jagom\u00e4e","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"},{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-345X","authenticated-orcid":false,"given":"Eero","family":"Vasar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Plaas","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"},{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/jmg.34.10.838","article-title":"Wolfram (DIDMOAD) Syndrome","volume":"34","author":"Barrett","year":"1997","journal-title":"J. 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