{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:03:42Z","timestamp":1753877022564,"version":"3.41.2"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Milken Institute\u2014Baszucki Brain Research Fund Bipolar Disorder Grant","award":["BD-0000000133"],"award-info":[{"award-number":["BD-0000000133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD, and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P\u2005=\u2005.031) and euthymic BD participants (P\u2005=\u2005.013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all P\u2005&amp;gt;\u2005.05). No differences were observed regarding MANF\/GRP78 protein or gene expression levels in postmortem tissue (P\u2005&amp;gt;\u2005.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Individuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf004","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T12:15:41Z","timestamp":1736770541000},"source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the mesencephalic astrocyte-derived neurotrophic factor\u2013endoplasmic reticulum stress pathway in mood disorders"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-460X","authenticated-orcid":false,"given":"Mohammad","family":"Ali","sequence":"first","affiliation":[{"name":"MiNDS Neuroscience Graduate Program, McMaster University , Hamilton, Ontario ,","place":["Canada"]},{"name":"Centre for Clinical Neurosciences, McMaster University , Hamilton, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Wollenhaupt-Aguiar","sequence":"additional","affiliation":[{"name":"Centre for Clinical Neurosciences, McMaster University , Hamilton, Ontario ,","place":["Canada"]},{"name":"Mood Disorders Treatment and Research Centre and Women\u2019s Health Concerns Clinic, St. Joseph\u2019s Healthcare Hamilton , Hamilton, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Clinical Neurosciences, McMaster University , Hamilton, Ontario ,","place":["Canada"]},{"name":"University of Ottawa Medical School , Ottawa, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahed","family":"Abu-Hijleh","sequence":"additional","affiliation":[{"name":"MiNDS Neuroscience Graduate Program, McMaster University , Hamilton, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolette","family":"Rigg","sequence":"additional","affiliation":[{"name":"MiNDS Neuroscience Graduate Program, McMaster University , Hamilton, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiane","family":"de Azevedo Cardoso","sequence":"additional","affiliation":[{"name":"IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University , Geelong, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Biomedical Sciences, McMaster University , Hamilton, Ontario ,","place":["Canada"]},{"name":"Michael G. 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