Investigation of the mesencephalic astrocyte-derived neurotrophic factor-endoplasmic reticulum stress pathway in mood disorders

被引：0

作者：

Ali, Mohammad ^{[1
,2
]}

Wollenhaupt-Aguiar, Bianca ^{[2
]}

Wang, Yifan ^{[2
,5
]}

Abu-Hijleh, Fahed ^{[1
]}

Rigg, Nicolette ^{[1
]}

Cardoso, Taiane de Azevedo ^{[6
]}

Ahmed, Imran ^{[7
,8
,9
]}

Gopalakrishnan, Ridhi ^{[2
]}

Jansen, Karen ^{[10
]}

Souza, Luciano Dias de Mattos ^{[10
]}

da Silva, Ricardo Azevedo ^{[10
]}

Mondin, Thaise Campos ^{[11
]}

Kapczinski, Flavio ^{[12
,13
,14
,15
]}

Moreira, Fernanda Pedrotti ^{[10
]}

Lofts, Andrew ^{[16
]}

Gwynne, William D. ^{[17
,18
]}

Hoare, Todd ^{[16
,19
]}

Mishra, Ram ^{[12
]}

Frey, Benicio N. ^{[2
,3
,4
,12
]}

机构：

[1] McMaster Univ, MiNDS Neurosci Grad Program, Hamilton, ON, Canada

[2] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada

[3] St Josephs Healthcare Hamilton, Mood Disorders Treatment & Res Ctr, Hamilton, ON, Canada

[4] St Josephs Healthcare Hamilton, Womens Hlth Concerns Clin, Hamilton, ON, Canada

[5] Univ Ottawa, Med Sch, Ottawa, ON, Canada

[6] Deakin Univ, Inst Mental & Phys Hlth & Clin Translat, Sch Med, IMPACT, Geelong, Vic, Australia

[7] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada

[8] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON, Canada

[9] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON, Canada

[10] Univ Catolica Pelotas, Dept Hlth & Behav, Pelotas, Brazil

[11] Univ Fed Pelotas, Dept Student Affairs, Pelotas, Brazil

[12] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada

[13] Univ Fed Rio Grande do Sul, Dept Psychiat, Porto Alegre, RS, Brazil

[14] Hosp Clin Porto Alegre, Lab Mol Psychiat, Porto Alegre, Brazil

[15] Inst Nacl Ciencia & Tecnol Translac Med, Porto Alegre, Brazil

[16] McMaster Univ, Sch Biomed Engn, Hamilton, ON L8S 4L8, Canada

[17] McMaster Univ, Dept Surg, West Hamilton, ON L8S 4L8, Canada

[18] McMaster Univ, Ctr Discovery Canc Res CDCR, West Hamilton, ON L8S 4L8, Canada

[19] McMaster Univ, Dept Chem Engn, West Hamilton, ON L8S 4L8, Canada

来源：

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY | 2025年 / 28卷 / 02期

关键词：

bipolar disorder; mood disorders; endoplasmic reticulum (ER) stress; MANF; UPR; MDD; GRP78; UNFOLDED PROTEIN RESPONSE; WHITE-MATTER INTEGRITY; BIPOLAR DISORDER; INFLAMMATION; RELIABILITY; DEMENTIA; CELLS; RISK;

D O I：

10.1093/ijnp/pyaf004

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: 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). Methods: 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. Results: Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P = .031) and euthymic BD participants (P = .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 > .05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (P > .05). Conclusions: 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.

引用

页数：10

共 47 条

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