Divergent changes in complement pathway gene expression in schizophrenia and bipolar disorder: Links to inflammation and neurogenesis in the subependymal zone.

Autor: Sager REH; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA., North HF; Neuroscience Research Australia, Randwick, NSW, Australia; Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia., Weissleder C; Mechanism and therapy for genetic brain diseases, Institut Imagine, Paris, France., Clearwater MS; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia., Walker AK; Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, Australia., Fullerton JM; Neuroscience Research Australia, Randwick, NSW, Australia; School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia., Webster MJ; Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD, USA., Shannon Weickert C; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA; Neuroscience Research Australia, Randwick, NSW, Australia; Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. Electronic address: c.shannonweickert@unsw.edu.au.
Jazyk: angličtina
Zdroj: Schizophrenia research [Schizophr Res] 2024 Nov 30; Vol. 275, pp. 25-34. Date of Electronic Publication: 2024 Nov 30.
DOI: 10.1016/j.schres.2024.11.005
Abstrakt: Deficits in neurogenesis markers in the subependymal zone (SEZ) are associated with elevated inflammation in schizophrenia and bipolar disorder. However, the extent to which complement factors are also changed in the SEZ of these major psychiatric disorders and their impact on neurogenesis remains poorly understood. We extracted RNA from the SEZ of 93 brains, including controls (n = 32), schizophrenia (n = 32), and bipolar disorder (n = 29) cases. Quantitative RT-PCR measured 13 complement transcripts encoding initiators, convertases, effectors or inhibitors. Differences in abundance were analysed by diagnosis and inflammatory subgroups (high- or low-inflammation), which were previously defined by SEZ cytokine and inflammation marker expression. Complement mRNAs C1QA (p = 0.011), C1QB (p < 0.001), C1R (p = 0.027), and Factor B (p = 0.025) were increased in high-inflammation schizophrenia versus low-inflammation controls. Conversely, high-inflammation bipolar cases had decreased C1QC (p = 0.011) and C3 (p = 0.003). Complement mRNAs C1R (SCZ, p = 0.010; BD, p = 0.047), C1S (SCZ, p = 0.026; BD, p = 0.017), and Factor B (BD, p = 0.025) were decreased in low-inflammation schizophrenia and bipolar subgroups versus low-inflammation controls. Complement inhibitors varied by subgroup: Factor H was increased in high-inflammation schizophrenia (p < 0.001), and CD59 in high-inflammation bipolar disorder (p = 0.020). Complement activator and inhibitor mRNAs were positively correlated with quiescent neural stem cell marker GFAPD (q < 0.05) but negatively with immature neuron markers DLX6-AS1 (q < 0.05) and DCX (q < 0.05). These findings suggest altered complement cascade expression in the SEZ in high- and low-inflammation schizophrenia and bipolar disorder, with opposite directional changes suggesting distinct molecular pathology. Complement activation may promote stem cell quiescence and reduce differentiation or survival of newborn neurons.
Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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