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

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Mohammad Ali, Bianca Wollenhaupt-Aguiar, Yifan Wang, Fahed Abu-Hijleh, Nicolette Rigg, Taiane de Azevedo Cardoso, Imran Ahmed, Ridhi Gopalakrishnan, Karen Jansen, Luciano Dias de Mattos Souza, Ricardo Azevedo da Silva, Thaise Campos Mondin, Flavio Kapczinski, Fernanda Pedrotti Moreira, Andrew Lofts, William D Gwynne, Todd Hoare, Ram Mishra, Benicio N Frey
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引用次数: 0

Abstract

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.

情绪障碍中脑星形胶质细胞源性神经营养因子-内质网应激通路的研究。
背景:双相情感障碍(BD)与细胞恢复能力受损有关。最近的研究表明,BD中未折叠蛋白反应(UPR)异常,UPR是细胞对内质网(ER)应激的反应。中脑星形胶质细胞源性神经营养因子(MANF)是一种营养因子,通过调节UPR降低内质网应激。本研究的目的是研究双相障碍和重度抑郁症(MDD)患者与健康对照组(HC)相比的MANF-ER应激途径。方法:检测BD、MDD和HC患者外周血中MANF蛋白浓度及MANF和GRP78基因表达(蛋白:40 BD、55 MDD、55 HC;基因表达:BD 52, MDD 61, HC 69)。在死后脑组织(20例BD, 20例MDD, 19例HC)中分析了MANF蛋白和GRP78基因的表达。采用ELISA法定量测定MANF蛋白,采用定量聚合酶链反应测定MANF和GRP78基因的表达。结果:与对照组(p=0.031)和健康型双相障碍患者(p=0.013)相比,抑郁状态双相障碍患者外周血MANF蛋白水平降低。与HC相比,无论情绪状态如何,抑郁症患者的MANF或GRP78基因表达均无显著差异(均p < 0.05)。死后组织中MANF/GRP78蛋白或基因表达水平无差异(p < 0.05)。结论:处于急性抑郁期的双相障碍患者外周血MANF水平降低,这可能意味着UPR异常,并支持双相障碍与内质网应激增加有关的观点。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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