Neuropathological implication of high blood bilirubin in patients and model rats with depression.

Autor: Gao Y; School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China. Electronic address: g2145010772@163.com., Ling Y; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Anhui Mental Health Center, Hefei, China. Electronic address: 15005661018@163.com., Li J; School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China. Electronic address: ljingjing0310@163.com., Xu Y; School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. Electronic address: 413271974@qq.com., Ge J; School of Pharmacy, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. Electronic address: gejinfang@ahmu.edu.cn., Xia Q; School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China. Electronic address: ahmcxqr@163.com.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2024 Sep; Vol. 215, pp. 111028. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1016/j.brainresbull.2024.111028
Abstrakt: Purpose: Elevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior.
Patients and Methods: Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively.
Results: Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress.
Conclusion: Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.
Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. and declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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